High frequencies of de novo CNVs in bipolar disorder and schizophrenia
Open accessAbstract
While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.
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- Findingown data
No significant associations were detected between de novo CNV regions and bipolar disorder in the case-control analysis.
“No significant associations were detected in bipolar disorder (Table S6A).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
In bipolar disorder and schizophrenia cohorts, de novo mutation rates were not higher in sporadic cases than in subjects with a positive family history.
“In BD and SCZ cohorts, rates of de novo mutation were not higher in sporadic cases as compared with subjects with a positive family history (Table S5).”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The family history information used to classify cases as familial or sporadic is accurate.
- Findingown data
The majority of de novo CNVs were not flanked by segmental duplications.
“By contrast, the majority of de novo CNVs were not flanked by SDs.”
Quote in the paperNot a substantial claim - Findingown data
About one-third (8/23) of de novo CNVs were flanked by segmental duplications at one or both boundaries.
“About one-third (8/23) of de novo CNVs in our study were flanked by segmental duplications (SDs) at one (6/23) or at both boundaries (2/23).”
Quote in the paperNot a substantial claim - Findingown data
No effect of age at onset on de novo CNV frequency was observed in schizophrenia.
“By contrast, we did not observe an effect of AAO on the frequency of de novo mutations in schizophrenia (Table 2, Figure 3B).”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
The case-control dataset did not provide significant support for enrichment of genes related to neural tube development or hindbrain development.
“The case-control data set did not provide significant support for an enrichment of genes related to neural tube development or hindbrain development.”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
De novo CNV frequency is significantly higher in bipolar disorder cases than in healthy controls (OR 4.8, 95% CI 1.4-16.0, p=0.009).
“Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR= 4.8 [1.4,16.0], p= 0.009).”
- Also stated in: § Results · plain
“The observed rate of de novo CNVs in bipolar disorder subjects was 4.3% (8/185), a significant enrichment compared with controls (p = 0.009, OR = 4.8 [1.4,16.0]).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Also stated in: § Results · plain
- Findingown data
De novo CNVs of intermediate size (10-100 kb) were detected at a rate of 0.7% (3/426) in controls, 1.7% (3/177) in schizophrenia, and 2.7% (5/185) in bipolar disorder.
“De novo CNVs of intermediate size (10–100 kb) were detected a rate of 3/426 (0.7%) in controls and at a rate of 3/177 (1.7%) in schizophrenia and 5/185 (2.7%) in bipolar disorder.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
Three categories-neural tube development, hindbrain development, and response to ethanol-were also enriched in permutation tests of de novo CNVs in cases and controls.
“Three were also found to be enriched based on permutation tests of de novo CNVs in cases and controls, including “neural tube development,” “hindbrain development,” and “response to ethanol” (Table 4).”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
De novo CNV frequency is significantly higher in schizophrenia cases than in healthy controls (OR 5.0, 95% CI 1.5-16.8, p=0.007).
“We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR= 5.0 [1.5,16.8], p= 0.007).”
- Also stated in: § Results · plain
“De novo CNVs were also detected at a significantly higher rate (8/177, 4.5%) in schizophrenia subjects than in controls (p = 0.007, OR = 5.0 [1.5,16.8]).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Also stated in: § Results · plain
- Findingown data
There was a trend of enrichment for large (≥500 kb) inherited duplications in familial bipolar disorder (OR=1.77, p=0.03).
“We observed a trend of enrichment for large (≥500 kb) inherited duplications in familial cases of bipolar disorder (OR = 1.77, p = 0.03, Table 3).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The family history information used to classify cases as familial or sporadic is accurate.
- Findingown data
No enrichment of inherited deletions was observed in familial bipolar disorder.
“We did not observe an enrichment of deletions in familial bipolar disorder.”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The family history information used to classify cases as familial or sporadic is accurate.
- Findingown data
Among bipolar disorder cases with age at onset ≤18, de novo CNV frequency is significantly higher than in controls (OR 6.3, 95% CI 1.7-22.6, p=0.006).
“De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR= 6.3 [1.7,22.6], p= 0.006).”
- Also stated in: § Results · plain
“After stratifying patients by age at onset ≤ 18, we observed a significantly higher rate of de novo CNVs in early-onset BD (p = 0.006, OR = 6.3 [1.7,22.6], Table 2).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The age at onset information used to define early-onset cases is accurate.
- Also stated in: § Results · plain
- Findingown data
In schizophrenia, three genomic regions were significantly associated in the case-control analysis.
“In schizophrenia, three genomic regions were significant (Table S6B), all corresponding to CNVs that have been previously implicated in schizophrenia at 3q29 (Mulle et al., 2010), 7q36.3 (Vacic et al., 2011), and 16p11.2 (McCarthy et al., 2009).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
The study detected and validated 23 de novo CNVs, including 14 deletions and 9 duplications.
“A total of 23 de novo CNVs were detected and validated in our study sample, including fourteen deletions and nine duplications (Table 1).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
The difference in age at onset between subjects with and without a de novo CNV was nominally significant (p=0.03) in a survival analysis.
“This difference was also nominally significant (p = 0.03) based on a survival analysis comparing AAO in subjects with or without a de novo CNV (Figure 3A).”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The age at onset information used to define early-onset cases is accurate.
- Findingown data
Based on DAVID analysis, eight functional categories were enriched among de novo CNVs in schizophrenia (p<0.05).
“Based on the primary analysis using DAVID, eight functional categories were enriched among de novo CNVs in SCZ (p < 0.05).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
Genes involved in neurodevelopment were not enriched among de novo CNVs in bipolar disorder or controls.
“Genes involved in neurodevelopment were not enriched among de novo CNVs in BD (Table 5) or in controls (Table S7).”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
The rate of de novo CNVs in healthy controls in this cohort is 0.9% (4/426).
“The rate of de novo mutation in controls was 0.9% (4/426).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
In an independent case-control dataset, two categories-synapse and Kelch-type beta propeller-were significantly enriched among rare variants in schizophrenia cases.
“Eight categories were tested in the case-control sample using the PLINK-CNV parametric test, and two categories, “synapse” and “Kelch-type beta propeller,” were significantly enriched among rare variants in cases (Table 4).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Findingown data
The overall validation rate for putative de novo CNVs was 16%, corresponding to 23 of 145 calls.
“The overall validation rate of putative de novo CNVs was 16% (23/145).”
Quote in the paperNot a substantial claim - Findingown data
The analysis identified 145 putative de novo CNVs among 788 subjects with bipolar disorder, schizophrenia, or control status.
“We identified 145 putative de novo CNVs in 788 subjects including BD, SCZ, and controls.”
Quote in the paperSubstantial claim - Findingown data
Categories enriched among de novo CNVs in bipolar disorder were related to cell proliferation and shape and phospholipid metabolism.
“By contrast, categories that were found to be enriched among de novo CNVs in BD were related to cell proliferation and shape and phospholipid metabolism (Table 5), the biological relevance of which is far from obvious.”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Interpretationown data
The inherited CNV results are consistent with a role for inherited CNVs in familial bipolar disorder, particularly large duplications.
“These results are consistent with a role for inherited CNVs in familial BD, particularly for large duplications; however, data from a much larger sample are needed to draw firm conclusions.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The family history information used to classify cases as familial or sporadic is accurate.
- Interpretationown data
The study's results provide significant evidence that de novo mutation is associated with bipolar disorder.
“These results provide significant evidence for an association of de novo mutation with bipolar disorder and confirm earlier reports of a high rate of de novo copy-number mutation in schizophrenia (Xu et al., 2008).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Interpretationown data
A small fraction of the heritability in schizophrenia can be found among intermediate-sized de novo structural variants.
“We conclude that a small fraction of the heritability in schizophrenia can be found among intermediate sized de novo structural variants.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Interpretationreasoning
The much greater effect size for de novo CNVs compared with inherited variants is consistent with de novo mutations having a higher proportion of risk alleles relative to neutral alleles.
“The much greater effect size for de novo CNVs as compared with inherited variants is consistent with de novo mutations having a much higher proportion of risk alleles relative to neutral alleles.”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Interpretationcitation
The study confirms earlier reports of a high rate of de novo copy-number mutation in schizophrenia.
“These results provide significant evidence for an association of de novo mutation with bipolar disorder and confirm earlier reports of a high rate of de novo copy-number mutation in schizophrenia (Xu et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Xu et al., 2008
Not checked in the free run.
- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Interpretationcitation
The study confirms previous findings that de novo CNVs occur at a significantly increased rate in individuals with schizophrenia.
“We also confirm previous findings that de novo CNVs occur at a significantly increased rate in individuals with schizophrenia (Xu et al., 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Xu et al., 2008
Not checked in the free run.
- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Premiseown data
The three significant schizophrenia regions correspond to CNVs previously implicated in schizophrenia at 3q29, 7q36.3, and 16p11.2.
“In schizophrenia, three genomic regions were significant (Table S6B), all corresponding to CNVs that have been previously implicated in schizophrenia at 3q29 (Mulle et al., 2010), 7q36.3 (Vacic et al., 2011), and 16p11.2 (McCarthy et al., 2009).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationcitation
The segmental-duplication-flanked de novo CNVs most likely arose by nonallelic homologous recombination.
“This class of CNV most likely occurred by nonallelic homologous recombination (NAHR) (Lupski, 1998).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lupski, 1998 source
Not checked in the free run.
- Interpretationown data
The study finds evidence consistent with earlier observations that rare CNVs in schizophrenia are enriched for neurodevelopmental and synaptic genes.
“While the strength of evidence supporting specific pathways differs between data sets, we do find evidence consistent with our earlier observations that there is an enrichment of “neurodevelopmental” and “synaptic” genes among rare CNVs in SCZ (Walsh et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Walsh et al., 2008 source
Not checked in the free run.
- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Interpretationown data
The study provides strong evidence implicating rare de novo CNVs in genetic risk for bipolar disorder.
“Here we find strong evidence implicating rare de novo CNVs in genetic risk for bipolar disorder.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Interpretationown data
The method had high sensitivity for detecting de novo CNVs across different size classes.
“These comparisons showed that our method had high sensitivity in identifying de novo CNVs in different size classes.”
Quote in the paperSubstantial claim - Interpretationown data
Pathway analysis of genes impacted by de novo CNVs in schizophrenia supports independent findings that rare CNVs in schizophrenia are enriched for synaptic and neurodevelopmental genes.
“Pathway analysis of genes impacted by de novo CNVs in SCZ lends support to independent findings from our group (Walsh et al., 2008) and others (Kirov et al., 2011) that rare CNVs in SCZ are enriched for genes that are related to synaptic function and other genes involved in neurodevelopment.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Walsh et al., 2008 source
Not checked in the free run.
- cites Kirov et al., 2011
Not checked in the free run.
- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Study design and conductown data
Adaptive filtering of confidence scores maintained the false-positive CNV call rate at 5% over a wide range of CNV sizes.
“The false-positive CNV call rate was controlled (maintained at 5%) for a wide range of CNV sizes by adaptive filtering of confidence scores (CSs), as described above.”
Quote in the paperSubstantial claim - Interpretationcitation
Preliminary findings and similar previous results suggest that early-onset mania may define a bipolar disorder subclass with greater contribution from rare alleles of large effect.
“These preliminary findings and similar results from previous studies (Priebe et al., 2011 and Zhang et al., 2009) suggest that individuals with an early onset of mania might constitute a subclass of bipolar disorder in which there is a greater contribution from rare alleles of large effect.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Priebe et al., 2011
Not checked in the free run.
- cites Zhang et al., 2009 source
Not checked in the free run.
- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The age at onset information used to define early-onset cases is accurate.
- Interpretationreasoning
The degree of enrichment of exonic point mutations in schizophrenia (0.73/exome in cases vs 0.32/exome in controls in the combined sample) is modest compared to the effect size for de novo CNVs.
“While the degree of enrichment of exonic point mutations in schizophrenia (0.73/exome in cases as compared with 0.32/exome in controls in the combined sample) is modest compared to the effect size for de novo CNVs, these results are nevertheless intriguing.”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Premisenone given
DAVID's enrichment test does not correct for CNV biases toward particular functional gene classes, especially large genes.
“The enrichment test performed within the DAVID software does not correct for certain biases of CNVs toward certain functional classes of genes and large genes in particular.”
Quote in the paperSubstantial claim - Study design and conductown data
Rare CNVs present in subjects and absent in parents were validated and fine mapped using a custom tiling-resolution CGH array.
“Rare CNVs that were present in subjects and not in their parents were subsequently validated and fine mapped using a custom tiling-resolution CGH array (Oxford Gene Technology) (Table S3.”
Quote in the paperSubstantial claim - Interpretationown data
The study's findings establish a contribution of rare CNVs and spontaneous mutation to risk for bipolar disorder.
“Our findings establish a contribution of rare CNVs and spontaneous mutation to risk for bipolar disorder.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Interpretationcitation
The study's family-history results contrast with earlier findings in autism and schizophrenia of higher de novo CNV rates in sporadic cases.
“These results contrast with earlier findings by our group and others in autism (Marshall et al., 2008 and Sebat et al., 2007) and schizophrenia (Xu et al., 2008) documenting a higher rate of CNVs in sporadic cases as compared with subjects who have a positive family history.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Marshall et al., 2008 source
Not checked in the free run.
- cites Sebat et al., 2007 source
Not checked in the free run.
- cites Xu et al., 2008
Not checked in the free run.
- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The family history information used to classify cases as familial or sporadic is accurate.
- Premisereasoning
Population CNVs are not an ideal control set for gene set enrichment because natural selection shapes their gene content, making them unrepresentative of random mutation.
“Naturally occurring variants in the population do not make the ideal control set for this analysis because the gene content of these CNVs is shaped by natural selection and is not likely to be representative of random mutation.”
Quote in the paperSubstantial claim
- May combine two claims. 20
- Classified as probably not a substantial claim. 28
May combine two claims.
Findingown dataNo significant enrichment of inherited deletions or duplications was observed in sporadic bipolar disorder or in schizophrenia.
“Likewise, we did not observe a significant enrichment of deletions or duplications in sporadic bipolar disorder or in schizophrenia (Table 3).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The family history information used to classify cases as familial or sporadic is accurate.
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataBreakpoint sequences were obtained for five deletions.
“Breakpoint sequences were obtained for five deletions (Table 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataDe novo CNVs in the study ranged from 15.1 to 7,178 kb, with a median size of 112 kb and a median of two genes.
“De novo CNVs ranged in size from 15.1 to 7,178 kb, with a median size of 112 kb, and contained a median of two genes.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataOf five deletion breakpoints, three junction sequences were in SINE repetitive elements and two had unique breakpoint sequences.
“Junction sequences of three out of five deletions were in short interspersed nuclear element (SINE) repetitive elements and two deletions had unique sequences at their breakpoints.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe median size of segmental-duplication-mediated de novo CNVs was 722 kb, and of non-SD-mediated de novo CNVs was 67 kb.
“Notably, the median size of SD and non-SD-mediated de novo CNVs was 722 kb and 67 kb respectively, consistent with previous studies that have found differences in CNV size related to the underlying mutational mechanism (Itsara et al., 2010 and Stefansson et al., 2008).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataA 1 bp insertion occurred at one of the deletion breakpoints.
“A 1 bp insertion occurred at one of the breakpoints (see underlined base in Figure 2I).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataInherited CNVs detected in this study included a 1q21.1 duplication in a bipolar disorder subject and a duplication and a deletion at 15q13.3 in bipolar disorder and schizophrenia subjects, respectively.
“Notably, inherited CNVs detected in this study included variants at loci that have been previously linked to schizophrenia (International Schizophrenia Consortium, 2008 and Stefansson et al., 2008), including a duplication at 1q21.1 in a subject with bipolar disorder and a duplication and a deletion at 15q13.3 detected in subjects with bipolar disorder and schizophrenia, respectively (Document S2,”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites International Schizophrenia Consortium, 2008
Not checked in the free run.
- cites Stefansson et al., 2008 source
Not checked in the free run.
- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
May combine two claims.
Findingown dataIn 45 autism spectrum disorder trios, the method detected and validated all three de novo CNVs from the previous study and found one additional novel de novo CNV of 38 kb.
“In 45 ASD trios we detected and validated all 3 de novo CNVs that were identified in our previous study and in addition, we identified one novel de novo CNV 38 kb in size (Table S8).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sebat et al., 2007 source
Not checked in the free run.
May combine two claims.
Findingown dataDAVID analysis found eight enriched categories for schizophrenia de novo CNVs, seven for bipolar disorder de novo CNVs, and nine for control de novo CNVs.
“Based on analysis using DAVID, eight categories were enriched among de novo CNVs in SCZ (Table 4), seven categories were enriched among de novo CNVs in BD (Table 5), and nine categories were enriched among de novo CNVs in controls (Table S7).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataThree of the four de novo events were shared between the two groups, and the one event unique to each group was smaller than 20 kb.
“Three out of four de novo events overlapped between two groups. One de novo event that was unique to each group was < 20 kb in size.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThe final set of rare CNVs comprised 3,856 calls in 788 offspring (bipolar disorder, schizophrenia, and controls) and 45 autism spectrum disorder subjects.
“This final rare CNV call sets consisted of 3,856 CNVs in 788 offspring including BD, SCZ, and controls and in 45 ASD subjects (Table S1).”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Findingown dataThe GRS score distributions separated first-degree relative pairs from unrelated pairs.
“Based on this test, first-degree relative pairs (i.e., mother-child and father-child) were clearly distinguishable from the distribution of GRS scores for unrelated individuals (i.e., mother-father pairs) as shown in Figure S2.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn the same 426 control trios, our group and Levy et al. each identified four validated de novo CNVs, giving an identical de novo CNV rate of 0.9%.
“Both groups identified four validated de novo CNVs in controls and therefore observed an identical rate (0.9%) of de novo CNVs in 426 controls.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Levy et al., 2011 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataValidation rates were highest for CNVs larger than 100 kb and lowest, at 3%, for CNVs smaller than 20 kb.
“As expected, the validation rate was highest for CNVs > 100 kb in size and lowest (3%) for CNVs that were < 20 kb in size.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataIntermediate-size CNVs may contribute to risk for these disorders, but they occur in only 2%-3% of cases and have a smaller relative effect size than large de novo CNVs.
“Based on these observations, intermediate-size CNVs may contribute to risk for these disorders; however, they occur in a small fraction (2%–3%) of cases, and the relative effect size is smaller than for large de novo CNVs.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe control de novo CNV rate of 0.9% is consistent with previous estimates ranging from 0.5% to 3%.
“This rate is consistent with estimates from previous studies ranging from 0.5% to 3% (Conrad et al., 2010, Itsara et al., 2010, Levy et al., 2011, Sebat et al., 2007 and Xu et al., 2008).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe size difference between SD-mediated and non-SD-mediated de novo CNVs is consistent with prior studies linking CNV size to mutational mechanism.
“Notably, the median size of SD and non-SD-mediated de novo CNVs was 722 kb and 67 kb respectively, consistent with previous studies that have found differences in CNV size related to the underlying mutational mechanism (Itsara et al., 2010 and Stefansson et al., 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Study design and conductnone givenThe high-density microarray platform used (2.1 million probes) provides good ascertainment of CNVs >10 kb, a substantial improvement in sensitivity over earlier studies of schizophrenia and autism.
“The high-density microarray platform used in this study (2.1 million probes) provides good ascertainment of CNVs > 10 kb, a substantial improvement in sensitivity over earlier studies of schizophrenia and autism.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationBased on this study, a contemporaneous study, and an earlier study, the overall frequency of de novo CNVs >10 kb is estimated to be approximately 4% in bipolar disorder and 5%-10% in schizophrenia.
“Based on our study, a contemporaneous study (Kirov et al., 2011), and an earlier study by our coauthor (Xu et al., 2008), we estimate that the overall frequency of de novo CNVs > 10 kb is approximately 4% in BD and 5%–10% in SCZ.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Kirov et al., 2011
Not checked in the free run.
- cites Xu et al., 2008
Not checked in the free run.
- Rests on an assumption: The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
- Rests on an assumption: The 788 trio cohort is representative of the broader bipolar disorder and schizophrenia populations.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductcitationThe enriched pathways were tested in rare CNVs from large independent case-control datasets: 8,290 schizophrenia cases and 7,431 controls from Vacic et al., a combined sample from three studies, and a bipolar disorder case-control set of 2,777 cases and 3,508 controls from BiGS.
“We extended our analysis of pathways identified in this study (Table 4 and Table 5, and S7) to rare CNVs from large case-controls studies of SCZ and BD. These included rare CNVs from 8,290 SCZ cases and 7,431 controls from Vacic et al. (2011), a combined sample of three studies from our group, MGS (Levinson et al., 2011), and the International Schizophrenia Consortium (International Schizophrenia”
Quote in the paperSubstantial claim0 of 3 sources checkedClassified as probably not a substantial claim.
Study design and conductnone givenStringent QC filters were applied to arrays and CNV calls to ensure that CNV ascertainment was consistent between subjects and their parents.
“Stringent QC filters were applied to arrays and CNV calls to ensure that the ascertainment of CNVs was consistent between subjects and their parents (see Supplemental Experimental Procedures and Table S1).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPreliminary studies have found evidence that the exomic burden of de novo point mutations is increased in schizophrenia.
“Indeed, preliminary studies of a small number of families have found evidence that the exomic burden of de novo point mutations is increased in schizophrenia (Girard et al., 2011 and Xu et al., 2011).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Girard et al., 2011 source
Not checked in the free run.
- cites Xu et al., 2011
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenSample coding and random-order hybridization were used to prevent plate effects.
“Samples were coded and hybridizations were done in random order to avoid any plate effects.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisereasoningDe novo CNV calls are more likely than inherited calls to contain technical errors, particularly false positives in offspring and false negatives in parents.
“While CNV calls that show mendelian patterns of inheritance (which is the overwhelming majority of CNVs in the genome) are quite reliable, the fraction of CNV calls that are present in offspring and not in parents are enriched for technical errors, in particular false-positive calls (in the offspring) and false-negative calls (in parents).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataParentage testing excluded 32 families, leaving 788 trios for analysis.
“Thirty-two families failed parentage testing, and the remaining 788 trios were included in our analysis.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenA pathway was considered enriched only if it reached nominal significance (p < 0.05) in both the case-only and case-control permutation tests.
“A category was defined as “enriched” if nominally significant (p < 0.05) by all case-only and case-control permutation tests.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataTwo permutation-based tests were used to correct for CNV biases: a case-only permutation test and a case-control enrichment test in PLINK.
“In order to correct for these biases we applied two permutation-based tests to the pathways found to be enriched by DAVID. First, we performed a case-only permutation-based test by constructing empirical null distributions that took the CNV size distribution and gene number into account.”
- Also stated in: § Gene Set Enrichment Analysis of De Novo CNVs · plain
“Second we applied a case-control CNV enrichment test implemented in PLINK”
Quote in the paperSubstantial claim- Also stated in: § Gene Set Enrichment Analysis of De Novo CNVs · plain
Classified as probably not a substantial claim.
Study design and conductown dataEvery putative de novo CNV was independently validated using a second custom tiling array platform.
“All putative de novo CNVs detected in our whole-genome scans were independently validated on second custom tiling array platform.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductreasoningRare CNVs overlapping known segmental duplications by more than 70% were excluded.
“Second, we removed rare CNVs which had > 70% overlap with known SDs from the UCSC hg18 Human Genome browser annotations.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Premisenone givenThe enrichment of technical errors in de novo CNV calls is greater for smaller CNVs.
“In addition, the enrichment of such errors is greater for smaller CNVs.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataParentage was verified with the Glaubitz Relationship Score using a >0.37 threshold and with Graphical Representation of Relationships.
“We applied a threshold of > 0.37 to define relatedness.”
- Also stated in: § Parentage Testing · plain
“Pairwise relationship of all subjects in 788 trios was confirmed using a second relatedness testing method, Graphical Representation of Relationships (GRR, http://www.sph.umich.edu/csg/abecasis/GRR/).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Glaubitz et al., 2003 source
Not checked in the free run.
- Also stated in: § Parentage Testing · plain
Classified as probably not a substantial claim.
Study design and conductown dataThe confidence-score thresholds were tuned within each CNV size class so that the overall rate of mendelian inconsistency was 5%.
“Thresholds for CS were then adjusted within each size class of CNV to achieve a 5% rate of mendelian inconsistency across all size classes (Figure S1).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataA small set of ASD trios, three carrying known de novo CNVs, was included as a positive control to confirm sensitivity of de novo detection methods.
“In addition, a small set of autism spectrum disorder (ASD) trios (n = 45), all of which had been included in a previous study (Sebat et al., 2007) and three of which carried known de novo CNVs, were included as a “positive control” to confirm the sensitivity of our methods for detecting de novo events.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sebat et al., 2007 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationPermutation-based tests were used to correct for the known bias of CNVs toward large genes in the functional enrichment analysis.
“Enrichment of functional classes of genes was tested using the DAVID software (http://david.abcc.ncifcrf.gov/), followed by two additional permutation-based tests to correct for the known bias of CNVs toward large genes (Raychaudhuri et al., 2010), one implemented as a case-only analysis and a second implemented as a case-control analysis in PLINK (http://pngu.mgh.harvard.edu/~purcell/plink/cnv.s”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Raychaudhuri et al., 2010 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenArrays with a derivative log2 ratio spread greater than 0.2 were repeated.
“Experiments with poor derivative log2 ratio spread (DLRS > 0.2) were repeated.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataFor control de novo CNVs, pathway enrichment significance was assessed with a single control-only permutation test.
“Pathway enrichment analysis was also applied to de novo CNVs in control, and significance was based on a single (control only) permutation test.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductreasoningA child's rare CNV was classified as inherited when either parent had a confidence score ≤0.04 and as de novo when both parents had a confidence score >0.04.
“Rare CNVs in children were called inherited if the CS was ≤ 0.04 in either of the two biological parents and de novo if CS was > 0.04 in both biological parents.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataPositive CNV calls were confirmed by manually inspecting log2 ratios in the child, mother, and father.
“Positive CNV calls were further verified by manual inspection of log2 ratios in the subject, mother, and father.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductreasoningParental false-negative calls were minimized by directly genotyping the CNV region with MeZOD and assigning parental genotypes from confidence scores.
“In order to minimize the number of false-negative calls in parents, the CNV region was directly genotyped using the MeZOD, and a confidence score was used to assign genotypes to the parents.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The clinical diagnoses of bipolar disorder, schizophrenia, and healthy control status in the trio cohort are accurate.
“Diagnoses of subjects included bipolar disorder (n = 185, including 107 with an age at onset ≤ 18), schizophrenia (n = 177), and healthy controls (n = 426).”
The paper relies on this without support.
The 788 trio cohort is representative of the broader bipolar disorder and schizophrenia populations.
“Our study sample included 788 subject-mother-father trios with confirmed parentage.”
The paper relies on this without support.
The family history information used to classify cases as familial or sporadic is accurate.
“We stratified subjects based on evidence of positive family history, defined as having a first-degree relative with a diagnosis of bipolar I, bipolar II, major depression, schizophrenia, schizoaffective disorder, autism, or intellectual disability.”
The paper relies on this without support.
The age at onset information used to define early-onset cases is accurate.
“After stratifying patients by age at onset ≤ 18, we observed a significantly higher rate of de novo CNVs in early-onset BD (p = 0.006, OR = 6.3 [1.7,22.6], Table 2).”
The paper relies on this without support.
The reference population of 4,081 unrelated subjects is representative of the general population for estimating CNV frequency.
“We determined the population frequency of CNVs detected in our study sample by comparison with CNV calls (based on ≥ 50% reciprocal overlap of its CNV length) from a larger reference population of 4,081 unrelated subjects analyzed in our laboratory using the same array platform.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Kirov et al. and Malhotra et al. observed a high rate of de novo CNVs in schizophrenia (5% in both) compared with controls, but neither found a significant difference between sporadic and familial cases.
“Subsequent studies by Kirov et al. (Kirov et al., 2011) and by our group (Malhotra et al., 2011), also observed a high rate of de novo CNVs in schizophrenia (5% in both studies) as compared with controls; however, neither study observed a significant difference in rate between in sporadic and famial cases.”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
Inherited or de novo CNVs are enriched in individuals with early-onset mania.
“The enrichment of inherited or de novo CNVs in subjects with an early onset of mania (Malhotra et al., 2011; Priebe et al., 2011; Zhang et al., 2009a) is consistent with the notion of distinct subtypes and suggest that individuals with an early onset of mania might constitute a subclass of bipolar disorder in which there is a greater contribution from rare alleles of large effect.”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
Current evidence suggests CNVs have a role in bipolar disorder, but large deletions in particular play a very limited role.
“Current evidence suggests that CNVs have a role to play (Malhotra et al., 2011), but some, particularly large deletions appear to play a very limited role (Grozeva et al., 2010; Malhotra et al., 2011).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
Early CNV studies suggest that rare variants play a role in bipolar disorder.
“Results from early CNV studies suggest that rare variants play a role in bipolar disorder (Malhotra et al., 2011; Priebe et al., 2011; Zhang et al., 2009a).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
Very few CNVs contributing to schizophrenia are also associated with bipolar disorder, with possible exceptions being 16p11.2 microduplications and 3q29 microdeletions.
“Notably, very few of the CNVs that contribute to risk for schizophrenia are also associated with bipolar disorder, the possible exceptions being microduplications of 16p11.2 (McCarthy et al., 2009) and microdeletions of 3q29 (Clayton-Smith et al., 2010; Malhotra et al., 2011), which have been reported in multiple cases (Table 1).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
De novo CNVs in bipolar disorder showed enrichment of genes involved in regulation of cell shape.
“We examined pathways enriched among de novo CNVs in bipolar disorder and observed an enrichment of genes involved in regulation of cell shape, but we did not observe a significant enrichment of genes involved in neuronal function or development (Malhotra et al., 2011).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
In bipolar disorder, de novo CNV frequency was 4.3%, significantly higher than the 0.09% found in healthy controls.
“Frequencies of de novo CNVs were significantly higher (4.3%) in bipolar disorder as compared with healthy individuals(0.09%).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
Rare CNVs in schizophrenia tend to affect genes involved in neuronal function, including synaptic activity and neurodevelopment.
“Early on, it was apparent that rare CNVs tended to impact genes involved in neuronal function (Walsh et al., 2008). These included functional categories related to synaptic activity and neurodevelopment (Malhotra et al., 2011; Walsh et al., 2008).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
Among bipolar disorder cases with onset before age 18, the de novo CNV rate was 5.6%, comparable to the 4.5% rate observed in schizophrenia using the same methods.
“The rate of de novo CNVs among cases with an age at onset younger than 18 was higher still (5.6%), and comparable to the rate we observed in schizophrenia (4.5%) using the same methods.”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
De novo mutations have consistently shown the strongest genetic effect.
“de novo mutations have consistently shown the strongest genetic effect (Kirov et al., 2011; Levy et al., 2011; Malhotra et al., 2011; Marshall et al., 2008; Sanders et al., 2011; Sebat et al., 2007; Xu et al., 2008).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
De novo CNVs in bipolar disorder did not show significant enrichment of genes involved in neuronal function or development.
“We examined pathways enriched among de novo CNVs in bipolar disorder and observed an enrichment of genes involved in regulation of cell shape, but we did not observe a significant enrichment of genes involved in neuronal function or development (Malhotra et al., 2011).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Malhotra et al., 2011
Control subjects had a frequency of 1%-2% de novo CNVs.
“Overall, 4.7% of trios had at least one de novo CNV, whereas control subjects had a frequency of 1%–2%.4,31,38”
From Convergence of genes and cellular pathways dysregulated in autism spectrum disorders (2014) · cites this paper as [38]
For BIP, there are reports of increased and similar SV burden in cases versus controls.
“For BIP, there are reports of increased 51–53 and similar SV burden in cases versus controls 54,55”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [53]
De novo SV may be relevant in BIP (OR=4.8), particularly in cases with earlier ages of onset (OR=6.3).
“De novo SV may be relevant in BIP (OR=4.8), particularly in cases with earlier ages of onset (OR=6.3). 53”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [53]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Early-onset age cutoff differs between sections
MinorThe abstract describes the enriched group as having onset before age 18, while the study defines early onset as age 18 or younger. The latter includes patients whose onset was at 18.
“De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR= 6.3 [1.7,22.6], p= 0.006).”
“After stratifying patients by age at onset ≤ 18, we observed a significantly higher rate of de novo CNVs in early-onset BD (p = 0.006, OR = 6.3 [1.7,22.6], Table 2).”
Cites
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795 · cited 11× · see citing works
“We evaluated the performance of our de novo CNV calling method by: i) analyzing a small set of 45 ASD trios included in our previous CNV study (Sebat et al., 2007) and, ii) by comparing results on validated control de novo CNVs identified by our group with results from a recent study(Levy et al.”
InfluentialSelf-citationThe Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,714 · see citing works
Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative
Merikangas, K. R., Jin, R., He, J.-P., Kessler, R. C., Lee, S., Sampson, N. A., Viana, M. C., Andrade, L. H., Hu, C., Karam, E. G., et al. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.12 · Cited by 2,627 · cited 1× · see citing works
“The lifetime prevalence of bipolar disorder in the general population is ~1% and the illness is associated with considerable morbidity and a high lifetime risk of suicide (Merikangas et al., 2011).”
Functional impact of global rare copy number variation in autism spectrum disorders
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., et al. (2010) · Nature · doi:10.1038/nature09146 · Cited by 2,013 · see citing works
Self-citationOrigins and functional impact of copy number variation in the human genome
The Wellcome Trust Case Control Consortium, Conrad, D. F., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., Aerts, J., Andrews, T. D., Barnes, C., et al. (2010) · Nature · doi:10.1038/nature08516 · Cited by 1,970 · cited 2× · see citing works
“This rate is consistent with estimates from previous studies ranging from 0.5% to 3% (Conrad et al., 2010, Itsara et al., 2010, Levy et al., 2011, Sebat et al., 2007 and Xu et al., 2008).”
InfluentialStructural Variation of Chromosomes in Autism Spectrum Disorder
Marshall, C. R., Noor, A., Vincent, J. B., Lionel, A. C., Feuk, L., Skaug, J., Shago, M., Moessner, R., Pinto, D., Ren, Y., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.12.009 · Cited by 1,815 · cited 12× · see citing works
“Studies from our group (McCarthy et al., 2009, Sebat et al., 2007, Vacic et al., 2011 and Walsh et al., 2008) and from multiple independent groups (International Schizophrenia Consortium, 2008, Pinto et al., 2010, Stefansson et al., 2008 and Xu et al., 2008) have now firmly established that rare CNVs contribute to gen…”
InfluentialRare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800 · cited 6× · see citing works
“Pathway analysis of genes impacted by de novo CNVs in SCZ lends support to independent findings from our group (Walsh et al., 2008) and others (Kirov et al., 2011) that rare CNVs in SCZ are enriched for genes that are related to synaptic function and other genes involved in neurodevelopment.”
InfluentialSelf-citationLarge recurrent microdeletions associated with schizophrenia.
GROUP, Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P. H., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., et al. (2008) · Nature · doi:10.1038/nature07229 · Cited by 1,745 · cited 3× · see citing works
“…Vacic et al., 2011 and Walsh et al., 2008) and from multiple independent groups (International Schizophrenia Consortium, 2008, Pinto et al., 2010, Stefansson et al., 2008 and Xu et al., 2008) have now firmly established that rare CNVs contribute to genetic risk for schizophrenia (SCZ) and autism…”
Self-citationRare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475 · see citing works
Self-citationPsychiatric GWAS Consortium Bipolar Disorder Working Group, Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., Edenberg, H. J., Nurnberger, J. I., Rietschel, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.943 · Cited by 1,344 · cited 1× · see citing works
“Robust support for one of these loci, the L-type calcium channel CACN1AC, has been obtained in a recent meta-analysis of 11,974 patients and 51,792 controls, along with new evidence for a second locus, ODZ4 (Sklar et al., 2011).”
Self-citationSanders, S. J., Ercan-Sencicek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D., Chu, S. H., Moreau, M. P., Gupta, A. R., Thomson, S. A., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.002 · Cited by 1,263 · cited 3× · see citing works
“De novo CNVs have consistently shown the strongest association with risk for autism (Itsara et al., 2010, Levy et al., 2011, Pinto et al., 2010 and Sanders et al., 2011) or schizophrenia (Xu et al., 2008), with a 5-to 10-fold enrichment in patients as compared with controls.”
The Heritability of Bipolar Affective Disorder and the Genetic Relationship to Unipolar Depression
McGuffin, P., Rijsdijk, F., Andrew, M., Sham, P., Katz, R., & Cardno, A. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.5.497 · Cited by 1,243 · cited 1× · see citing works
“The rate of concordance for monozygotic twins is 40%, compared with a 5% rate in dizygotic twins (Kendler et al., 1995, Kieseppä et al., 2004 and McGuffin et al., 2003), and risk among the first-degree relatives of individuals with BD is ten-fold greater than risk among the general population…”
Wellcome Trust Case Control Consortium, Ferreira, M. A. R., O'Donovan, M. C., Meng, Y. A., Jones, I. R., Ruderfer, D. M., Jones, L., Fan, J., Kirov, G., Perlis, R. H., et al. (2008) · Nature Genetics · doi:10.1038/ng.209 · Cited by 1,237 · cited 2× · see citing works
“Early studies implicated a few common variants with modest effects (Baum et al., 2008; Ferreira et al., 2008).”
Self-citationLi, C., & Wong, W. H. (2001) · Genome biology · doi:10.1186/gb-2001-2-8-research0032 · Cited by 977 · see citing works
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“(D) UCSC genome browser tracks of known genes are shown to scale with a tra by nonallelic homologous recombination (NAHR) (Lupski, 1998).”
Kirov, G., Pocklington, A. J., Holmans, P., Ivanov, D., Ikeda, M., Ruderfer, D., Moran, J., Chambert, K., Toncheva, D., Georgieva, L., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.154 · Cited by 844 · cited 4× · see citing works
“These early observations have not been universally replicated (Kirov et al., 2011; Pinto et al., 2010).”
InfluentialStrong association of de novo copy number mutations with sporadic schizophrenia
Xu, B., Roos, J. L., Levy, S., van Rensburg, E. J., Gogos, J. A., & Karayiorgou, M. (2008) · Nature Genetics · doi:10.1038/ng.162 · Cited by 813 · cited 16× · see citing works
“While the primary disease focus of this study was BD, the inclusion of an additional schizophrenia cohort served first to replicate the one previous study of de novo CNVs in SCZ (Xu et al., 2008) and second to enable a valid comparison of patterns of de novo CNVs in BD with another disorder.”
InfluentialSelf-citationRare de novo and transmitted copy-number variation in autistic spectrum disorders
Levy, D., Ronemus, M., Yamrom, B., Lee, Y.-H., Leotta, A., Kendall, J., Marks, S., Lakshmi, B., Pai, D., Ye, K., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.015 · Cited by 712 · cited 8× · see citing works
“…of our de novo CNV calling method by: i) analyzing a small set of 45 ASD trios included in our previous CNV study (Sebat et al., 2007) and, ii) by comparing results on validated control de novo CNVs identified by our group with results from a recent study(Levy et al., 2011) by Mike Wigler's group.”
InfluentialSelf-citationMicroduplications of 16p11.2 are associated with schizophrenia
Wellcome Trust Case Control Consortium, McCarthy, S. E., Makarov, V., Kirov, G., Addington, A. M., McClellan, J., Yoon, S., Perkins, D. O., Dickel, D. E., Kusenda, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.474 · Cited by 711 · cited 4× · see citing works
“2 (McCarthy et al., 2009) and 3q29 (Clayton-Smith et al., 2010, Mulle et al., 2010 and Quintero-Rivera et al., 2010) confer risk for multiple psychiatric disorders, and two studies have found preliminary evidence implicating both in BD (McCarthy et al., 2009 and Quintero-Rivera et al., 2010).”
InfluentialSelf-citationDefining Clinical Phenotypes of Juvenile Mania
Leibenluft, E., Charney, D. S., Towbin, K. E., Bhangoo, R. K., & Pine, D. S. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.3.430 · Cited by 685 · cited 1× · see citing works
“We followed strict DSM-IV guidelines, including duration criteria for manic episodes, to diagnose BD in youth (Leibenluft et al., 2003) as well as in adults.”
Self-citationExome sequencing supports a de novo mutational paradigm for schizophrenia
Xu, B., Roos, J. L., Dexheimer, P. J., Boone, B. E., Plummer, B., Levy, S., Gogos, J. A., & Karayiorgou, M. (2011) · Nature Genetics · doi:10.1038/ng.902 · Cited by 461 · cited 1× · see citing works
“Indeed, preliminary studies of a small number of families have found evidence that the exomic burden of de novo point mutations is increased in schizophrenia (Girard et al., 2011 and Xu et al., 2011).”
Self-citationIncreased exonic de novo mutation rate in individuals with schizophrenia
Girard, S. L., Gauthier, J., Noreau, A., Xiong, L., Zhou, S., Jouan, L., Dionne-Laporte, A., Spiegelman, D., Henrion, E., Diallo, O., et al. (2011) · Nature Genetics · doi:10.1038/ng.886 · Cited by 438 · cited 2× · see citing works
“Indeed, preliminary studies of a small number of families have found evidence that the exomic burden of de novo point mutations is increased in schizophrenia (Girard et al., 2011 and Xu et al., 2011).”
Levinson, D. F., Duan, J., Oh, S., Wang, K., Sanders, A. R., Shi, J., Zhang, N., Mowry, B. J., Olincy, A., Amin, F., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.10060876 · Cited by 434 · cited 5× · see citing works
“We performed an analysis of CNVs in SNP genotyping data from multiple casecontrol studies, including the Bipolar Genome Study (BiGS) and Molecular Genetics of Schizophrenia (MGS) study (see Supplemental Experimental Procedures).”
InfluentialThe genetics of bipolar disorder
Barnett, J. H., & Smoller, J. W. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.03.080 · Cited by 407 · see citing works
High Concordance of Bipolar I Disorder in a Nationwide Sample of Twins
Kieseppä, T., Partonen, T., Haukka, J. K., Kaprio, J. A., & Lönnqvist, J. K. (2004) · American Journal of Psychiatry · doi:10.1176/ajp.161.10.1814 · Cited by 406 · cited 1× · see citing works
“The rate of concordance for monozygotic twins is 40%, compared with a 5% rate in dizygotic twins (Kendler et al., 1995, Kieseppä et al., 2004 and McGuffin et al., 2003), and risk among the first-degree relatives of individuals with BD is ten-fold greater than risk among the general population…”
Smith, E. N., Bloss, C. S., Badner, J. A., Barrett, T., Belmonte, P. L., Berrettini, W., Byerley, W., Coryell, W., Craig, D., Edenberg, H. J., et al. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.43 · Cited by 363 · cited 2× · see citing works
“, 2011), and the International Schizophrenia Consortium (International Schizophrenia Consortium, 2008), and a BD casecontrol data set consisting of 2,777 cases and 3,508 controls from BiGS study (Smith et al., 2009).”
Self-citationAdjustment of genomic waves in signal intensities from whole-genome SNP genotyping platforms
Diskin, S. J., Li, M., Hou, C., Yang, S., Glessner, J., Hakonarson, H. H., Bućan, M., Maris, J. M., & Wang, K. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn556 · Cited by 350 · cited 1× · see citing works
“Finally, log2 ratios were corrected for genomic wave effects due to regional correlations with GC content based on the fitted linear regression model (Diskin et al., 2008).”
Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia
Vacic, V., McCarthy, S., Malhotra, D., Murray, F., Chou, H.-H., Peoples, A., Makarov, V., Yoon, S., Bhandari, A., Corominas, R., et al. (2011) · Nature · doi:10.1038/nature09884 · Cited by 337 · see citing works
Self-citationDe novo rates and selection of large copy number variation
Itsara, A., Wu, H., Smith, J. D., Nickerson, D. A., Romieu, I., London, S. J., & Eichler, E. E. (2010) · Genome Research · doi:10.1101/gr.107680.110 · Cited by 328 · cited 6× · see citing works
“5% to 3% (Conrad et al., 2010; Itsara et al., 2010; Levy et al., 2011; Sebat et al., 2007; Xu et al., 2008).”
InfluentialMicrodeletions of 3q29 confer high risk for schizophrenia
Mulle, J. G., Dodd, A. F., McGrath, J. A., Wolyniec, P. S., Mitchell, A. A., Shetty, A. C., Sobreira, N. L., Valle, D., Rudd, M. K., Satten, G., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.07.013 · Cited by 223 · cited 2× · see citing works
“2 (McCarthy et al., 2009) and 3q29 (Clayton-Smith et al., 2010, Mulle et al., 2010 and Quintero-Rivera et al., 2010) confer risk for multiple psychiatric disorders, and two studies have found preliminary evidence implicating both in BD (McCarthy et al., 2009 and Quintero-Rivera et al., 2010).”
Grozeva, D. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.25 · Cited by 192 · cited 3× · see citing works
“However, two subsequent studies did not support these findings (Grozeva et al., 2010 and McQuillin et al., 2011).”
InfluentialXu, B., Woodroffe, A., Rodriguez‐Murillo, L., Roos, J. L., van Rensburg, E. J., Abecasis, G. R., Gogos, J. A., & Karayiorgou, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908584106 · Cited by 154 · cited 1× · see citing works
“…family-based studies of autism (Levy et al., 2011, Marshall et al., 2008, Sanders et al., 2011 and Sebat et al., 2007) and schizophrenia (Xu et al., 2008 and Xu et al., 2009) that have found a strong and robust genetic effect for de novo mutations and a weaker genetic effect for inherited variants.”
Self-citationSingleton deletions throughout the genome increase risk of bipolar disorder
Zhang, D., Cheng, L., Qian, Y., Alliey-Rodriguez, N., Kelsoe, J. R., Greenwood, T., Nievergelt, C., Barrett, T. B., McKinney, R., Schork, N., et al. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.144 · Cited by 148 · cited 5× · see citing works
“These preliminary findings and similar results from previous studies (Priebe et al., 2011 and Zhang et al., 2009) suggest that individuals with an early onset of mania might constitute a subclass of bipolar disorder in which there is a greater contribution from rare alleles of large effect.”
InfluentialSelf-citationMania in late life: focus on age at onset
Young, R. C., & Klerman, G. L. (1992) · American Journal of Psychiatry · doi:10.1176/ajp.149.7.867 · Cited by 143 · see citing works
Prospects for inferring pairwise relationships with single nucleotide polymorphisms
Glaubitz, J. C., Rhodes, O. E., & Dewoody, J. A. (2003) · Molecular Ecology · doi:10.1046/j.1365-294x.2003.01790.x · Cited by 136 · cited 3× · see citing works
“Based on this test, first-degree relative pairs (i.e., mother-child and father-child) were clearly distinguishable from the distribution of GRS scores for unrelated individuals (i.e., mother-father pairs) as shown in Figure S2.”
InfluentialKendler, K. S., Pedersen, N. L., Neale, M. C., & Mathé, A. A. (1995) · Behavior Genetics · doi:10.1007/bf02197180 · Cited by 134 · cited 1× · see citing works
“The rate of concordance for monozygotic twins is 40%, compared with a 5% rate in dizygotic twins (Kendler et al., 1995, Kieseppä et al., 2004 and McGuffin et al., 2003), and risk among the first-degree relatives of individuals with BD is ten-fold greater than risk among the general population…”
Raychaudhuri, S., Korn, J. M., McCarroll, S. A., The International Schizophrenia Consortium, Altshuler, D., Sklar, P., Purcell, S., & Daly, M. J. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001097 · Cited by 131 · cited 1× · see citing works
“…(http://david.abcc.ncifcrf.gov/), followed by two additional permutationbased tests to correct for the known bias of CNVs toward large genes (Raychaudhuri et al., 2010), one implemented as a case-only analysis and a second implemented as a case-control analysis in PLINK…”
Sparse representation and Bayesian detection of genome copy number alterations from microarray data
Piqué-Regi, R., Monso-Varona, J., Ortega, A., Seeger, R. C., Triche, T. J., & Asgharzadeh, S. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btm601 · Cited by 128 · cited 1× · see citing works
“, 2007) and GADA (Pique-Regi et al., 2008).”
Baum, A. E., Hamshere, M., Green, E., Cichon, S., Rietschel, M., Nöthen, M. M., Craddock, N. J., & McMahon, F. J. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.16 · Cited by 114 · cited 2× · see citing works
“Early studies implicated a few common variants with modest effects (Baum et al., 2008; Ferreira et al., 2008).”
Self-citationUnsupervised segmentation of continuous genomic data
Day, N., Hemmaplardh, A., Thurman, R. E., Stamatoyannopoulos, J. A., & Noble, W. S. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm096 · Cited by 109 · see citing works
Quintero‐Rivera, F., Sharifi‐Hannauer, P., & Martínez-Agosto, J. A. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33573 · Cited by 93 · cited 1× · see citing works
“2 (McCarthy et al., 2009) and 3q29 (Clayton-Smith et al., 2010, Mulle et al., 2010 and Quintero-Rivera et al., 2010) confer risk for multiple psychiatric disorders, and two studies have found preliminary evidence implicating both in BD (McCarthy et al., 2009 and Quintero-Rivera et al., 2010).”
Priebe, L., Degenhardt, F. A., Herms, S., Haenisch, B., Mattheisen, M., Nieratschker, V, Weingarten, M., Witt, S., Breuer, R., Paul, T., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.8 · Cited by 84 · cited 3× · see citing works
“Two studies have demonstrated an enrichment of rare CNVs in patients with bipolar disorder (Priebe et al., 2011 and Zhang et al., 2009) as compared with healthy controls.”
Self-citationDifferent familial transmission patterns in bipolar I disorder with onset before and after age 25
Grigoroiu‐Serbanescu, M., Martinez, M., Nöthen, M. M., Grinberg, M., Sima, D., Propping, P., Marinescu, E., & Hrestic, M. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.10047 · Cited by 83 · cited 1× · see citing works
“Also consistent with this notion is a previous study (Grigoroiu-Serbanescu et al., 2001), which found that segregation of early-onset BD in families was consistent with major gene effects, while familial segregation of late-onset BD was consistent with a multifactorial etiology.”
Self-citationThe bipolar disorder phenome database: a resource for genetic studies
Potash, J. B., Toolan, J., Steele, J., Miller, E. B., Pearl, J., Zandi, P. P., Schulze, T. G., Kassem, L., Simpson, S. G., Lopez, V., et al. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.06122045 · Cited by 80 · cited 2× · see citing works
“probably due to a high degree of genetic heterogeneity and considerable phenotypic heterogeneity of clinical populations (Potash et al., 2007).”
Self-citationClayton-Smith, J., Giblin, C., Smith, R. A., Dunn, C., & Willatt, L. (2010) · Clinical Dysmorphology · doi:10.1097/mcd.0b013e32833a1e3c · Cited by 64 · see citing works
Further evidence for age of onset being an indicator for severity in bipolar disorder
Schulze, T. G., Müller, D. J., Krauß, H., et al. (2002) · Journal of Affective Disorders · doi:10.1016/s0165-0327(01)00306-8 · Cited by 48 · see citing works
Self-citationMcQuillin, A., Bass, N., Anjorin, A., Lawrence, J., Kandaswamy, R., Lydall, G., Moran, J., Sklar, P., Purcell, S., & Gurling, H. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2010.221 · Cited by 47 · cited 2× · see citing works
“However, two subsequent studies did not support these findings (Grozeva et al., 2010 and McQuillin et al., 2011).”
InfluentialA comparison of the age of onset of bipolar I and bipolar II outpatients
Benazzi, F. (1999) · Journal of Affective Disorders · doi:10.1016/s0165-0327(99)00083-x · Cited by 45 · see citing works
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Benefits and limitations of genome-wide association studies
Tam, V., Patel, N. K., Turcotte, M., Bossé, Y., Paré, G., & Meyre, D. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0127-1 · Cited by 2,092 · see citing works
De novo mutations in schizophrenia implicate synaptic networks
Fromer, M., Pocklington, A. J., Kavanagh, D. H., Williams, H. J., Dwyer, S., Gormley, P., Georgieva, L., Rees, E., Palta, P., Ruderfer, D. M., et al. (2014) · Nature · doi:10.1038/nature12929 · Cited by 1,617 · see citing works
Genetic architectures of psychiatric disorders: the emerging picture and its implications
Sullivan, P. F., Daly, M. J., & O'Donovan, M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3240 · Cited by 1,177 · see citing works
Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
Marshall, C. R., Howrigan, D. P., Merico, D., Thiruvahindrapuram, B., Wu, W., Greer, D. S., Antaki, D., Shetty, A., Holmans, P. A., Pinto, D., et al. (2017) · Nature Genetics · doi:10.1038/ng.3725 · Cited by 1,058 · see citing works
“…that CNVs contribute to risk for SCZ: genome-wide enrichment of rare deletions and duplications in SCZ cases relative to controls 2, 3 , a higher rate of de novo CNVs in cases relative to controls 4–6 , and association evidence implicating a small number of specific loci (Supplementary Table 1).”
Self-citationConvergence of genes and cellular pathways dysregulated in autism spectrum disorders
Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L., Thiruvahindrapuram, B., Xu, X., Ziman, R., Wang, Z., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.03.018 · Cited by 969 · see citing works
“7% of trios had at least one de novo CNV, whereas control subjects had a frequency of 1%– 2%.(4,31,38) The average length of de novo events in our affected subjects (1.”
BackgroundCNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics
Malhotra, D., & Sebat, J. (2012) · Cell · doi:10.1016/j.cell.2012.02.039 · Cited by 854 · see citing works
Self-citationVieta, E., Berk, M., Schulze, T. G., Carvalho, A. F., Suppes, T., Calabrese, J. R., Gao, K., Miskowiak, K. W., & Grande, I. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.8 · Cited by 891 · see citing works
Self-citationPhenotypic impact of genomic structural variation: insights from and for human disease
Weischenfeldt, J., Symmons, O., Spitz, F., & Korbel, J. O. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3373 · Cited by 648 · see citing works
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Whole-Genome Sequencing in Autism Identifies Hot Spots for De Novo Germline Mutation
Michaelson, J. J., Shi, Y., Gujral, M., Zheng, H., Malhotra, D., Jin, X., Jian, M., Liu, G., Greer, D., Bhandari, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.11.019 · Cited by 544 · see citing works
“Based on experience from our earlier CNV-based studies of DNM (Malhotra et al., 2011; Nord et al., 2011; Sebat et al., 2007), an unfiltered set of putative DNMs is highly enriched for errors.”
Self-citationSynaptic dysregulation in a human iPS cell model of mental disorders
Wen, Z., Nguyen, H. N., Guo, Z., Lalli, M. A., Wang, X., Su, Y., Kim, N.-S., Yoon, K.-J., Shin, J., Zhang, C., et al. (2014) · Nature · doi:10.1038/nature13716 · Cited by 549 · see citing works
Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia
Genovese, G., Fromer, M., Stahl, E. A., Ruderfer, D. M., Chambert, K., Landén, M., Moran, J. L., Purcell, S. M., Sklar, P., Sullivan, P. F., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4402 · Cited by 444 · see citing works
A hierarchical causal taxonomy of psychopathology across the life span.
Lahey, B. B., Krueger, R. F., Rathouz, P. J., Waldman, I. D., & Zald, D. H. (2017) · Psychological Bulletin · doi:10.1037/bul0000069 · Cited by 443 · see citing works
“Other studies similarly indicate that some rare copy number variants and other structural variants are nonspecifically associated with multiple mental disorders (Bergen et al., 2012; Ionita-Laza et al., 2014; Levinson et al., 2011; Malhotra et al., 2011; Sanders et al., 2011).”
BackgroundDe novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia
Xu, B., Ionita-Laza, I., Roos, J. L., Boone, B., Woodrick, S., Sun, Y., Levy, S., Gogos, J. A., & Karayiorgou, M. (2012) · Nature Genetics · doi:10.1038/ng.2446 · Cited by 442 · see citing works
Self-citationGenetics and genomics of psychiatric disease
Geschwind, D. H., & Flint, J. (2015) · Science · doi:10.1126/science.aaa8954 · Cited by 424 · see citing works
Large-scale genomics unveils the genetic architecture of psychiatric disorders
Gratten, J., Wray, N. R., Keller, M. C., & Visscher, P. M. (2014) · Nature Neuroscience · doi:10.1038/nn.3708 · Cited by 363 · see citing works
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Self-citationSchizophrenia and the neurodevelopmental continuum:evidence from genomics
Owen, M. J., & O’Donovan, M. C. (2017) · World Psychiatry · doi:10.1002/wps.20440 · Cited by 326 · see citing works
Genetic Relationships Between Schizophrenia, Bipolar Disorder, and Schizoaffective Disorder
Cardno, A. G., & Owen, M. J. (2014) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu016 · Cited by 275 · see citing works
The genetics of bipolar disorder
Gordovez, F. J. A., & McMahon, F. J. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0634-7 · Cited by 268 · see citing works
Self-citationEbler, J., Ebert, P., Clarke, W. E., Rausch, T., Audano, P. A., Houwaart, T., Mao, Y., Korbel, J. O., Eichler, E. E., Zody, M. C., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01043-w · Cited by 277 · see citing works
The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders
Grayson, D. R., & Guidotti, A. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.125 · Cited by 267 · see citing works
Protein tyrosine phosphatases PTPδ, PTPσ, and LAR: presynaptic hubs for synapse organization
Takahashi, H., & Craig, A. M. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.06.002 · Cited by 257 · see citing works
Copy number variation in schizophrenia in Sweden
Szatkiewicz, J., O'Dushlaine, C., Chen, G., Chambert, K., Moran, J. L., Neale, B. M., Fromer, M., Ruderfer, D. M., Akterin, S., Bergen, S. E., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.40 · Cited by 240 · see citing works
A High-Resolution Enhancer Atlas of the Developing Telencephalon
Visel, A., Taher, L., Girgis, H., May, D., Golonzhka, O., Hoch, R. V., McKinsey, G. L., Pattabiraman, K., Silberberg, S. N., Blow, M. J., et al. (2013) · Cell · doi:10.1016/j.cell.2012.12.041 · Cited by 257 · see citing works
“evidence that noncoding sequence variants, as well as copynumber variation in coding and noncoding portions of the genome, have important impacts on a wide spectrum of disorders, including bipolar disorder, schizophrenia, autism, intellectual disability, and epilepsy (Cooper et al., 2011; Durbin et al., 2010; Internat…”
Doherty, J. L., & Owen, M. J. (2014) · Genome Medicine · doi:10.1186/gm546 · Cited by 228 · see citing works
“singleton deletions and de novo CNVs have been found to occur at a higher rate in bipolar disorder cases than in controls, particularly in early onset cases [67,68].”
BackgroundIdentification of Pathways for Bipolar Disorder: A Meta-analysis
Nurnberger, J. I., Koller, D. L., Jung, J., Edenberg, H. J., Foroud, T., Guella, I., Vawter, M. P., & Kelsoe, J. R. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.176 · Cited by 234 · see citing works
Self-citationLanz, T. A., Reinhart, V., Sheehan, M. J., Rizzo, S. J. S., Bove, S. E., James, L. C., Volfson, D., Lewis, D. A., & Kleiman, R. J. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0492-8 · Cited by 209 · see citing works
Loss-of-Function Variants in Schizophrenia Risk and SETD1A as a Candidate Susceptibility Gene
Takata, A., Xu, B., Ionita-Laza, I., Roos, J. L., Gogos, J. A., & Karayiorgou, M. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.043 · Cited by 204 · see citing works
Self-citationNovel Findings from CNVs Implicate Inhibitory and Excitatory Signaling Complexes in Schizophrenia
Pocklington, A. J., Rees, E., Walters, J. T. R., Han, J., Kavanagh, D. H., Chambert, K. D., Holmans, P., Moran, J. L., McCarroll, S. A., Kirov, G., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.04.022 · Cited by 193 · see citing works
“, 2014), which often occur as de novomutations (Kirov et al., 2012; Malhotra et al., 2011; Xu et al., 2008).”
BackgroundDiverse types of genetic variation converge on functional gene networks involved in schizophrenia
Gilman, S. R., Chang, J., Xu, B., Bawa, T. S., Gogos, J. A., Karayiorgou, M., & Vitkup, D. (2012) · Nature Neuroscience · doi:10.1038/nn.3261 · Cited by 200 · see citing works
Self-citationMilekic, M. H., Xin, Y., O’Donnell, A., Kumar, K. K., Bradley-Moore, M., Malaspina, D., Moore, H., Brunner, D., Ge, Y., Edwards, J., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.84 · Cited by 190 · see citing works
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Self-citationCopy number variation in bipolar disorder
Green, E., Rees, E., Walters, J., Gordon‐Smith, K., Forty, L., Grozeva, D., Moran, J. L., Sklar, P. B., Ripke, S., Chambert, K. D., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.174 · Cited by 183 · see citing works
“…BD cases, 17,18 that an increased rate of CNVs occurs in early-onset BD cases, 20 that the frequency of de novo CNVs are signi fi cantly more frequent in BD cases (with an onset below 18 years of age) than controls 21 and that the rate of de novo CNVs in BD are intermediate between SZ and controls.”
BackgroundGene expression imputation across multiple brain regions provides insights into schizophrenia risk
Huckins, L. M., Murray, R. M., Dobbyn, A. L., Ruderfer, D. M., Hoffman, G. E., Wang, W., Pardiñas, A. F., Rajagopal, V. M., Als, T. D., Nguyen, H. T., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0364-4 · Cited by 193 · see citing works
Madison, J. M., Zhou, F., Nigam, A., Hussain, A. H., Barker, D., Nehme, R., van der Ven, K., Hsu, J. Y., Wolf, P., Fleishman, M., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.7 · Cited by 174 · see citing works
“Of the input seed list of 53 differentially expressed genes, 43 were mappable by DAPPLE while a subset of genes that were also differentially expressed ( C4ORF45, CACNG8, FNIP2, HLA-B, IRX3, NKX2.”
Recent genetic findings in schizophrenia and their therapeutic relevance
Harrison, P. J. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881114553647 · Cited by 186 · see citing works
“It is thus notable that schizophrenia genes are also enriched for ARC genes (Fromer et al., 2014; Glessner et al., 2010; Lips et al., 2012; Malhotra et al., 2011; Purcell et al., 2014) and for those involved in other aspects of synaptic transmission (Kenny et al., 2014; Lips et al., 2012; Owen et…”
BackgroundGenetics of Schizophrenia: Overview of Methods, Findings and Limitations
Henriksen, M. G., Nordgaard, J., & Jansson, L. B. (2017) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2017.00322 · Cited by 169 · see citing works
“…found elevated levels of rare CNVs in patients with schizophrenia compared to controls (International Schizophrenia Consortium, 2008; Xu et al., 2008; International Schizophrenia Consortium et al., 2009; Malhotra et al., 2011; Szatkiewicz et al., 2014; Chang et al., 2016; Ruderfer et al., 2016).”
BackgroundCNVs in neuropsychiatric disorders
Kirov, G. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv253 · Cited by 159 · see citing works
“About 5% of SZ probands have a de novo CNV (29,30).”
BackgroundLAR-RPTPs: synaptic adhesion molecules that shape synapse development
Um, J. W., & Ko, J. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.07.004 · Cited by 164 · see citing works
Mullin, A. P., Gokhale, A., Moreno-De-Luca, A., Sanyal, S., Waddington, J. L., & Faúndez, V. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.108 · Cited by 165 · see citing works
Impacts of Variation in the Human Genome on Gene Regulation
Haraksingh, R., & Snyder, M. P. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.07.015 · Cited by 162 · see citing works
Gu, F., Chauhan, V. P. S., Kaur, K., Brown, W. T., LaFauci, G., Węgiel, J., & Chauhan, A. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.68 · Cited by 161 · see citing works
Lin, G. N., Corominas, R., Lemmens, I., Yang, X., Tavernier, J., Hill, D. E., Vidal, M., Sebat, J., & Iakoucheva, L. M. (2015) · Neuron · doi:10.1016/j.neuron.2015.01.010 · Cited by 155 · see citing works
“…Sebat et al., 2007), schizophrenia (SCZ) (Consortium, 2008; Kirov et al., 2009; Stefansson et al., 2008; Walsh et al., 2008), bipolar disorder (BD) (Malhotra et al., 2011), developmental delay (DD) (Cooper et al., 2011), attention deficit hyperactivity disorder (ADHD) (Lionel et al., 2011), and…”
BackgroundLionel, A. C., Vaags, A. K., Sato, D., Gazzellone, M. J., Mitchell, E. B., Chen, H. Y., Costain, G., Walker, S., Egger, G., Thiruvahindrapuram, B., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt056 · Cited by 162 · see citing works
“Higher resolution microarray and sequencing scans have detected smaller ultra-rare single gene CNVs and/or truncating point mutations affecting certain specific genes in both schizophrenia and ASD patient cohorts, such as NRXN1 (15,19), SHANK3 (27,28), CNTNAP2 (62,63), ASTN2 (64–66), A2BP1 (67,68), DPP6 (54,68,69), DP…”
BackgroundFernandez, B. A., & Scherer, S. W. (2017) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2017.19.4/sscherer · Cited by 160 · see citing works
Genetic Determinants of Depression: Recent Findings and Future Directions
Dunn, E. C., Brown, R. C., Dai, Y., Rosand, J., Nugent, N. R., Amstadter, A. B., & Smoller, J. W. (2015) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000054 · Cited by 158 · see citing works
“De novo CNVs—those that are present in offspring but not in either parent—have been shown to be important risk factors for several neuropsychiatric disorders— namely autism,(115,116) schizophrenia,(117,118) and bipolar disorder.(119) After conducting a systematic literature search of PubMed for articles published by D…”
BackgroundExplaining additional genetic variation in complex traits
Robinson, M. R., Wray, N. R., & Visscher, P. M. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.02.003 · Cited by 147 · see citing works
Clinically relevant copy number variations detected in cerebral palsy
Oskoui, M., Gazzellone, M. J., Thiruvahindrapuram, B., Zarrei, M., Andersen, J. C., Wei, J., Wang, Z., Wintle, R. F., Marshall, C. R., Cohn, R. D., et al. (2015) · Nature Communications · doi:10.1038/ncomms8949 · Cited by 152 · see citing works
Lopes, A. M., Aston, K. I., Thompson, E. E., Carvalho, F., Gonçalves, J., Huang, N., Matthiesen, R., Noordam, M. J., Quintela, I., Ramu, A., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003349 · Cited by 142 · see citing works
“We obtained lists of rare deletions, left panel, from the Utah and WTCCC control cohorts and, right panel, from cohorts of developmental delay (DECIPHER) [66], autism [67], schizophrenia [68], bipolar disorder [66,68], and spermatogenic impairment (this study).”
MethodCopy number variation in obsessive-compulsive disorder and tourette syndrome: A cross-disorder study
McGrath, L. M., Yu, D., Marshall, C., Davis, L. K., Thiruvahindrapuram, B., Li, B., Cappi, C., Gerber, G., Wolf, A., Schroeder, F. A., et al. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2014.04.022 · Cited by 141 · see citing works
High-resolution copy number variation analysis of schizophrenia in Japan
Kushima, I., Aleksić, B., Nakatochi, M., Shimamura, T., Shiino, T., Yoshimi, A., Kimura, H., Takasaki, Y., Wang, C., Xing, J., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.88 · Cited by 132 · see citing works
Wang, S., Mandell, J. D., Kumar, Y., Sun, N., Morris, M. T., Arbelaez, J., Nasello, C., Dong, S., Duhn, C., Zhao, X., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.082 · Cited by 119 · see citing works
“2-13.3 have been observed in ASD (Sanders et al., 2015), schizophrenia (Georgieva et al., 2014; Malhotra et al., 2011), and epilepsy (Epilepsy Phenome/Genome Project Epi4K Consortium, 2015).”
Influential1q21.1 Microduplication expression in adults
Dolcetti, A., Silversides, C. K., Marshall, C. R., Lionel, A. C., Stavropoulos, D. J., Scherer, S. W., & Bassett, A. S. (2012) · Genetics in Medicine · doi:10.1038/gim.2012.129 · Cited by 126 · see citing works
The genetic variability and commonality of neurodevelopmental disease
Coe, B. P., Girirajan, S., & Eichler, E. E. (2012) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31327 · Cited by 124 · see citing works
“Schizophrenia: all sites n ¼ 4,168 [The International Schizophrenia Consortium, 2008; Malhotra et al., 2011], 15q13.”
BackgroundInfluentialSZDB: A Database for Schizophrenia Genetic Research
Wu, Y., Yao, Y., & Luo, X. (2016) · Schizophrenia Bulletin · doi:10.1093/schbul/sbw102 · Cited by 113 · see citing works
Genetic contributions to bipolar disorder: current status and future directions
O’Connell, K. S., & Coombes, B. J. (2021) · Psychological Medicine · doi:10.1017/s0033291721001252 · Cited by 115 · see citing works
“2 was first described as a de novo CNV for BD (Kirov, 2015; Malhotra et al., 2011) and this association was replicated in a larger genome-wide analysis (Green et al.”
Kataoka, M., Matoba, N., Sawada, T., Kazuno, A.-A., Ishiwata, M., Fujii, K., Matsuo, K., Takata, A., & Kato, T. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.69 · Cited by 104 · see citing works
Regulation of Recombination and Genomic MaintenancePreprint
Heyer, W. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016501 · Cited by 94 · see citing works
“Moreover, de novo point mutant and CNVs hotspots have been identified in patients with autism spectrum disorder as well as bipolar disease and schizophrenia (Malhotra et al. 2011; Michaelson et al. 2012).”
BackgroundGenetic Basis of Intellectual Disability
Ellison, J. W., Rosenfeld, J. A., & Shaffer, L. G. (2012) · Annual Review of Medicine · doi:10.1146/annurev-med-042711-140053 · Cited by 103 · see citing works
Control of neural circuit formation by leucine-rich repeat proteins
de Wit, J., & Ghosh, A. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.07.004 · Cited by 93 · see citing works
Reconsideration of bipolar disorder as a developmental disorder: Importance of the time of onset
Geoffroy, P. A., Étain, B., Scott, J. L., Henry, C., Jamain, S., Leboyer, M., & Bellivier, F. (2013) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2013.03.006 · Cited by 99 · see citing works
“Finally, two recent whole-genome analyses of copy number variations (CNVs, resulting from deletions and duplications of chromosome regions) identified microdeletions and microduplications in certain regions that were specifically associated with EOBD (Priebe et al., 2011 ; Malhotra et al., 2011).”
BackgroundExome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes
Guipponi, M., Santoni, F. A., Setola, V., Gehrig, C., Rothärmel, M., Cuenca, M., Guillin, O., Dikeos, D. G., Georgantopoulos, G., Papadimitriou, G. N., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0112745 · Cited by 89 · see citing works
“However, subsequent studies confirming a higher rate of de novo CNVs among individuals with SCZ compared with controls did not reveal a significant difference between individuals with sporadic or familial SCZ [17, 18].”
ResultAssessing the utility of intermediate phenotypes for genetic mapping of psychiatric disease
Flint, J., Timpson, N. J., & Munafo, M. R. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.007 · Cited by 93 · see citing works
The Role of the Eukaryotic Translation Initiation Factor 4E (eIF4E) in Neuropsychiatric Disorders
Amorim, I. S., Lach, G., & Gkogkas, C. G. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00561 · Cited by 93 · see citing works
The genomics of schizophrenia: update and implications
Giusti‐Rodríguez, P., & Sullivan, P. F. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66031 · Cited by 95 · see citing works
Essential genetic findings in neurodevelopmental disorders
Cardoso, A. R., Lopes‐Marques, M., Silva, R. M., Serrano, C., Amorim, A., Prata, M. J., & Azevedo, L. (2019) · Human Genomics · doi:10.1186/s40246-019-0216-4 · Cited by 87 · see citing works
The balancing act of GABAergic synapse organizers
Ko, J., Choii, G., & Um, J. W. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.01.004 · Cited by 86 · see citing works
De novo CNVs in bipolar affective disorder and schizophrenia
Georgieva, L., Rees, E., Moran, J. L., Chambert, K. D., Milanova, V. K., Craddock, N. J., Purcell, S., Sklar, P. B., McCarroll, S. A., Holmans, P., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu379 · Cited by 87 · see citing works
Ching, C., Gutman, B., Sun, D.-Q., Reina, J. E. V., Ragothaman, A., Isaev, D., Zavaliangos-Petropulu, A., Lin, A., Jonas, R., Kushan, L., et al. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19060583 · Cited by 77 · see citing works
“Although elevated rates of bipolar disorder have not been reported in large studies of 22q11DS (2, 37), the correlation between subcortical patterns in 22q11DS with psychosis and other disordersmay reflect the underlying genetic overlap between schizophrenia, bipolar disorder, major depression, and other psychiatric i…”
BackgroundA genetic model for neurodevelopmental disease
Coe, B. P., Girirajan, S., & Eichler, E. E. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.04.007 · Cited by 79 · see citing works
Gokhale, A., Larimore, J., Werner, E., So, L., Moreno-De-Luca, A., Lese-Martin, C., Lupashin, V. V., Smith, Y., & Faundez, V. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5640-11.2012 · Cited by 85 · see citing works
“…that if dysbindin is part of a molecular pathway contributing to or affected by schizophrenia, then genes encoding dysbindin interactors should be significantly represented among those genes with structural variants associated with schizophrenia risk, such as SNAP29 (Malhotra et al., 2011).”
BackgroundIonita‐Laza, I., Xu, B., Makarov, V., Buxbaum, J. D., Roos, J. L., Gogos, J. A., & Karayiorgou, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309475110 · Cited by 82 · see citing works
“Carriers of large (≥30 kb) rare de novo CNVs were excluded based on prior CNV scans of the same datasets (8, 9).”
BackgroundSelf-citationNoor, A., Lionel, A. C., Cohen‐Woods, S., Moghimi, N., Rucker, J., Fennell, A., Thiruvahindrapuram, B., Kaufman, L., Degagne, B., Wei, J., et al. (2014) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32232 · Cited by 81 · see citing works
New Ethical Issues for Genetic Counseling in Common Mental Disorders
Gershon, E. S., & Alliey‐Rodriguez, N. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12121558 · Cited by 85 · see citing works
Self-citationLi, Y., Zhang, P., Choi, T.-Y., Park, S. K., Park, H., Lee, E., Lee, D., Roh, J. D., Mah, W., Kim, R., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.002 · Cited by 79 · see citing works
Gazzellone, M. J., Zarrei, M., Burton, C. L., Walker, S., Uddin, M., Shaheen, S. M., Coste, J., Rajendram, R., Schachter, R. J., Colasanto, M., et al. (2016) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-016-9170-9 · Cited by 77 · see citing works
Mowry, B. J., & Gratten, J. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.34 · Cited by 81 · see citing works
Choi, Y., Nam, J., Whitcomb, D. J., Song, Y. S., Kim, D., Jeon, S., Um, J. W., Lee, S.-G., Woo, J., Kwon, S., et al. (2016) · Scientific Reports · doi:10.1038/srep26676 · Cited by 76 · see citing works
Cappi, C., Hounie, A. G., Mariani, D., Diniz, J. B., Silva, A. R. T., Reis, V. N. D. S., Busso-Lopes, A. F., Silva, A. G., Fidalgo, F., Rogatto, S. R., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110198 · Cited by 79 · see citing works
“The main CNVs associated with psychiatric disorders have generally been rare variants in genes involved in synaptogenesis, neuronal and axonal mobility, protein degradation via the ubiquitin-proteasome system (ubiquitin signaling), protein complexes and postsynaptic signaling [11,12,38–48].”
BackgroundIdentification of Neuropsychiatric Copy Number Variants in a Health Care System Population
Martin, C. L., Wain, K. E., Oetjens, M. T., Tolwinski, K., Palen, E., Hare-Harris, A. E., Habegger, L., Maxwell, E. K., Reid, J. G., Walsh, L. K., et al. (2020) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.2159 · Cited by 70 · see citing works
Charney, A. W., Stahl, E. A., Green, E., Chen, C., Moran, J. L., Chambert, K., Belliveau, R. A., Forty, L., Gordon‐Smith, K., Lee, P. H., et al. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.12.009 · Cited by 68 · see citing works
Self-citationNeuroanatomical phenotypes in a mouse model of the 22q11.2 microdeletion
Ellegood, J., Markx, S., Lerch, J. P., Steadman, P. E., Genç, C., Provenzano, F. A., Kushner, S. A., Henkelman, R. M., Karayiorgou, M., & Gogos, J. A. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.112 · Cited by 70 · see citing works
Self-citationRees, E., O’Donovan, M. C., & Owen, M. J. (2014) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2014.07.001 · Cited by 72 · see citing works
The role of genetics and genomics in clinical psychiatry
Hoehe, M. R., & Morris-Rosendahl, D. J. (2018) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2018.20.3/mhoehe · Cited by 66 · see citing works
Narla, S. T., Lee, Y. W., Benson, C. A., Sarder, P., Brennand, K., Stachowiak, E. K., & Stachowiak, M. K. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2016.12.012 · Cited by 59 · see citing works
“…variants in schizophrenia is an enrichment of those that are rare (b1% minor allele frequency) and large (N100 kb) CNVs (International Schizophrenia, 2008; Malhotra et al., 2011; Walsh et al., 2008), and those that occur de novo (Kirov et al., 2012; Malhotra et al., 2011; Xu et al., 2008).”
BackgroundMaya, I., Sharony, R., Yacobson, S., Kahana, S., Yeshaya, J., Tenne, T., Agmon‐Fishman, I., Cohen-Vig, L., Goldberg, Y., Berger, R., et al. (2017) · Genetics in Medicine · doi:10.1038/gim.2017.89 · Cited by 63 · see citing works
Rediscovering the value of families for psychiatric genetics research
Glahn, D. C., Nimgaonkar, V. L., Raventós, H., Rojas, J. C., McIntosh, A. M., Thomson, P. A., Jablensky, A. V., McCarthy, N. S., Charlesworth, J., Blackburn, N. B., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0073-x · Cited by 58 · see citing works
Self-citationGenetics of psychiatric disorders in the GWAS era: an update on schizophrenia
Schwab, S. G., & Wildenauer, D. B. (2013) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-013-0450-z · Cited by 61 · see citing works
“[41] were able to confirm this finding, even though slightly lower de novo mutation rates in schizophrenic patients (5.”
ResultCSMD3 is Associated with Tumor Mutation Burden and Immune Infiltration in Ovarian Cancer Patients
Lü, N., Liu, J., Xu, M., Liang, J., Wang, Y., Wu, Z., Xing, Y. T., & Diao, F. (2021) · International Journal of General Medicine · doi:10.2147/ijgm.s335592 · Cited by 48 · see citing works
Escudero, I., & Johnstone, M. (2014) · Current Psychiatry Reports · doi:10.1007/s11920-014-0502-8 · Cited by 61 · see citing works
Implications of Genetic Findings for Understanding Schizophrenia
Owen, M. J. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs103 · Cited by 58 · see citing works
Structural basis of SALM5-induced PTPδ dimerization for synaptic differentiation
Lin, Z., Liu, J., Ding, H., Xu, F., & Liu, H. (2018) · Nature Communications · doi:10.1038/s41467-017-02414-2 · Cited by 53 · see citing works
De Novo Mutation in Schizophrenia
Rees, E., Kirov, G., O’Donovan, M. C., & Owen, M. J. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs047 · Cited by 57 · see citing works
“2%.(12,13) Evidence from case-control studies now supports association between SZ and CNVs at more than 10 genomic loci (table 1),(3,15) and de novo occurrence has been observed at all strongly supported SZ CNV loci.”
BackgroundResultInfluentialKalkman, H. O. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.07.008 · Cited by 57 · see citing works
Genetics of Complex Traits in Psychiatry
Gelernter, J. E. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.08.005 · Cited by 55 · see citing works
“Sequencing can also identify other kinds of variants, e.g., CNVs.”
BackgroundInfluentialTranslational genomics and beyond in bipolar disorder
Zhang, C., Xiao, X., Li, T., & Li, M. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0782-9 · Cited by 51 · see citing works
Genome-wide copy number variation analysis in adult attention-deficit and hyperactivity disorder
Ramos‐Quiroga, J. A., Sánchez‐Mora, C., Casas, M., Iris Garcia-martinez, A., Bosch, R., Nogueira, M., Montse Corrales, F., Gloria Palomar, A., Vidal, R., Coll-Tané, M., et al. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.10.022 · Cited by 55 · see citing works
“Recent work, however, strengthens the hypothesis that copy number variations (CNVs) encompassing relatively large genomic regions might contribute to the susceptibility of different psychiatric disorders such as ADHD (Kirov et al., 2008; Malhotra et al., 2011; Schizophrenia, 2008; Stefansson et al., 2008; Walsh et al.…”
BackgroundKushima, I., Nakatochi, M., Aleksić, B., Okada, T., Kimura, H., Kato, H., Morikawa, M., Inada, T., Ishizuka, K., Torii, Y., et al. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.04.003 · Cited by 55 · see citing works
Bramon, E., Pirinen, M., Strange, A., Lin, K., Freeman, C., Bellenguez, C., Su, Z., Band, G., Pearson, R. D., Vukcevic, D., et al. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.03.033 · Cited by 51 · see citing works
Self-citation
- Authors
- Malhotra, D., McCarthy, S., Michaelson, J. J., Vacic, V., Burdick, K. E., Yoon, S., Cichon, S., Corvin, A., Gary, S., Gershon, E. S., Gill, M., Karayiorgou, M., Kelsoe, J. R., Krastoshevsky, O., Krause, V., Leibenluft, E., Levy, D. L., Makarov, V., Bhandari, A., Malhotra, A. K., McMahon, F. J., Nöthen, M. M., Potash, J. B., Rietschel, M., Schulze, T. G., & Sebat, J.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- University of California San Diego (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of Bonn (DE)
- Trinity College Dublin (IE)
- University of Chicago (US)
- Columbia University (US)
- McLean Hospital (US)
- National Institutes of Health (US)
- Northwell Health (US)
- University of Iowa (US)
- Heidelberg University (DE)
- University of Göttingen (DE)
- Corresponding author
- Sebat, Jonathan
- ORCID
- Malhotra, Dheeraj
- Michaelson, Jacob J.
- Vacic, Vladimir
- Burdick, Katherine E.
- Cichon, Sven
- Corvin, Aiden
- Gershon, Elliot S.
- Gill, Michael
- Karayiorgou, Maria
- Kelsoe, John R.
- Leibenluft, Ellen
- Levy, Deborah L.
- Makarov, Vladimir
- Bhandari, Abhishek
- Malhotra, Anil K.
- McMahon, Francis J.
- Nöthen, Markus M.
- Potash, James B.
- Rietschel, Marcella
- Schulze, Thomas G.
- Sebat, Jonathan
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 72
- Issue
- 6
- Pages
- 951-963
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3921625
- OpenAlex
- W2151834457
- Cited by
- 325
- References
- 50
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 8 · 2023: 10 · 2022: 17 · 2021: 11 · 2020: 21 · 2019: 34 · 2018: 15 · 2017: 17 · 2016: 21 · 2015: 39 · 2014: 52 · 2013: 36 · 2012: 31
- FWCI
- 23.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 594 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- DZNE Pub (submittedVersion)
- GRO (submittedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- Wellcome Trust (072894)
- National Institutes of Health (Z99 MH999999, 5r01mh071523-05)
- National Institute of Mental Health (MH061399, ZIAMH002778, R01MH061399, MH076431, MH071523, R01-MH071523, R01MH076431)
- National Human Genome Research Institute (P41HG004222, HG04222)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- de novo copy number variants, bipolar disorder, schizophrenia, neuropsychiatric disorders, trios, age of onset, genetic risk, spontaneous mutation, mood disorders
- MeSH terms
- Adolescent, Adult, Bipolar Disorder, Child, Female, Humans, Male, Schizophrenia, Genetic Variation, Case-Control Studies, Genome-Wide Association Study, Young Adult, DNA Copy Number Variations
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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