CoChat
Sign Up
Cited by 76Genomic variations and chromosomal abnormalitiesGenetics and Neurodevelopmental DisordersSchizophrenia research and treatment

Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice

Open access
Jønch, Aia Elise, Douard, Elise, Moreau, Clara, Van Dijck, Anke, Passeggeri, Marzia, Kooy, Frank, Puechberty, Jacques, Campbell, Carolyn +20 more·2019·Journal of Medical Genetics
DOI 10.1136/jmedgenet-2018-105879PMC PMC6817694
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: The 15q11.2 deletion is frequently identified in the neurodevelopmental clinic. Case–control studies have associated the 15q11.2 deletion with neurodevelopmental disorders, and clinical case series have attempted to delineate a microdeletion syndrome with considerable phenotypic variability. The literature on this deletion is extensive and confusing, which is a challenge for genetic counselling. The aim of this study was to estimate the effect size of the 15q11.2 deletion and quantify its contribution to neurodevelopmental disorders. Methods: We performed meta-analyses on new and previously published case–control studies and used statistical models trained in unselected populations with cognitive assessments. We used new (n=241) and previously published (n=150) data from a clinically referred group of deletion carriers. 15q11.2 duplications (new n=179 and previously published n=35) were used as a neutral control variant. Results: The deletion decreases IQ by 4.3 points. The estimated ORs and respective frequencies in deletion carriers for intellectual disabilities, schizophrenia and epilepsy are 1.7 (3.4%), 1.5 (2%) and 3.1 (2.1%), respectively. There is no increased risk for heart malformations and autism. In the clinically referred group, the frequency and nature of symptoms in deletions are not different from those observed in carriers of the 15q11.2 duplication suggesting that most of the reported symptoms are due to ascertainment bias. Conclusions: We recommend that the deletion should be classified as ‘pathogenic of mild effect size’. Since it explains only a small proportion of the phenotypic variance in carriers, it is not worth discussing in the developmental clinic or in a prenatal setting.

AI snapshot

Written from the paper’s full text.

TL;DR

The 15q11.2 BP1–BP2 deletion has a mild effect on cognition, decreasing IQ by about 4.3 points, and confers small or uncertain risks for neurodevelopmental and medical conditions. The authors recommend classifying it as “pathogenic of mild effect size” and not discussing it in the developmental clinic or prenatal setting.

Key findings

  • The deletion decreases IQ by 4.3 points (95% CI 6.5 to 2.03), equivalent to 0.28 z-scores, and translates into a 4% risk for intellectual disability versus 2% in the general population.
  • Estimated ORs and frequencies in deletion carriers were 1.7 (3.4%) for intellectual disabilities, 1.5 (2%) for schizophrenia, and 3.1 (2.1%) for epilepsy; there was no increased risk for heart malformations or autism.
  • In the clinically referred group, symptom frequencies in deletion carriers were not different from those in 15q11.2 duplication carriers: ID 42.3% vs 35.2%, ASD 12.9% vs 13.6%, epilepsy 15.3% vs 14.2%, and CHD 8.9% vs 5.7%, suggesting most reported symptoms are due to ascertainment bias.
  • The authors recommend classifying the deletion as “pathogenic of mild effect size” and state it is not worth discussing in the developmental clinic or prenatal setting.

Methods

  • Meta-analyses of new and previously published case–control studies, plus statistical models trained in unselected populations with cognitive assessments, using UK Biobank controls (151,619 individuals) and DECIPHER data (28,970 cases).
  • Clinically referred carrier groups included 391 deletion carriers (326 probands and 65 relatives) and 214 duplication carriers (176 probands and 38 relatives), combining new data (deletions n=241; duplications n=179) and previously published data (deletions n=150; duplications n=35).
  • Analyses included Fisher’s exact tests, random-effects meta-analyses, logistic regression for de novo occurrence, and pLI-based models; frequencies were computed by multiplying relative risk by general-population prevalence.

Limitations

  • Stated: estimates derive from case–control studies and statistical models trained in unselected populations; different unselected cohorts may yield slightly different deletion prevalences and change estimates, and early case–control studies grossly underestimated deletion frequency due to very small control groups.
  • Stated: the statistical model estimates small individual-gene effects and could underestimate the overall deletion effect; case–control association studies do not clearly rank which symptoms drive enrichment in disease cohorts.
  • Evident from the text: clinically referred case series are strongly affected by ascertainment bias, as shown by the similar symptom frequencies in deletion and neutral duplication carriers.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/jmedgenet-2018-105879

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

31 of 41 cited sources checked · 16 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The 15q11.2 deletion is associated with schizophrenia (OR 1.8).

    “a mild enrichment of the deletion is observed in individuals with schizophrenia (OR 1.8),2”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [2] source

      The Gene CNV association section reports a schizophrenia association for deletions at 15q13.3, not 15q11.2. Searches of our copy for 15q11.2 and an odds ratio of 1.8 found no passage establishing the claimed enrichment; the two loci cannot be treated as interchangeable. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
  • Premisecitation

    The 15q11.2 deletion is associated with learning disabilities (OR 4.4).

    “learning disabilities (OR 4.4, dyslexia and dyscalculia combined).5”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [5] Ulfarsson, 2017, 15q11.2 CNV affects cognitive, structural and functional correlates of dyslexia and dyscalculia, Transl Psychiatry source
  • Findingown data

    The 15q11.2 deletion is significantly enriched in the SJCHU CMA database (OR 1.9, 95% CI 1.5 to 2.4) compared with UK Biobank.

    “The deletion is significantly enriched in the SJCHU (OR 1.9, 95% CI 1.5 to 2.4) and OUH CMA database (OR 3.1, 95% CI 1.6 to 5.7), compared with the deletion prevalence from the UK BIOBANK (0.36%, 544/151619)16 (table 2).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [16] Kendall, 2017, Cognitive performance among carriers of pathogenic copy number variants: analysis of 152,000 UK Biobank subjects, Biol Psychiatry source

      The Results report 151,659 UK Biobank samples passing quality control, and the CNV Calling Criteria include 15q11.2 deletions. But our copy does not give the cited deletion prevalence of 0.36% (544/151,619) or the SJCHU comparison and odds ratio; it directs readers to a separate Excel file for locus-specific frequencies (CNV Breakpoints and Frequencies, Table S2). The citation is attached to the UK Biobank baseline, not clearly to the citing authors’ enrichment calculation. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Premisecitation

    More than 200 15q11.2 deletion carriers have been reported in clinical series with mild, moderate and severe neurodevelopmental symptoms as well as malformations.

    “More than 200 15q11.2 deletion carriers have been reported in clinical series with mild, moderate and severe neurodevelopmental symptoms as well as malformations leading authors to delineate a microdeletion syndrome with considerable phenotypic variability9 and incomplete penetrance.10”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [9] source

      The Abstract reviews clinical features from about 200 deletion carriers, and Table 5 in §2.5 includes a series totaling 216 carriers. The Introduction and Results describe variable neurodevelopmental findings and congenital anomalies, but the review does not classify carriers as having mild, moderate, and severe neurodevelopmental symptoms. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [10] source
  • Findingown data

    The meta-analysis of CHD case-control studies shows an OR of 4.96 when the small control groups from the original publications are used.

    “Our meta-analysis of CHD case–control studies6–8 shows an OR of 4.96 when the small control groups from the original publications are used (figure 1).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [6] Geng J , Picker J , Zheng Z , Zhang X , Wang J , Hisama F , Brown DW , Mullen MP , Harris D , Stoler J , Seman A , Miller DT , Fu Q , Roberts AE , Shen Y . Chromosome microarray testing for patients with congenital heart defects reveals novel disease causing loci and high diagnostic yield. BMC Genomics 2014;15.doi:10.1186/1471-2164-15-1127 source

      The Methods section (Statistical analysis; page unavailable) describes Fisher’s exact tests comparing CNV frequencies, not a meta-analysis of CHD case–control studies. The Discussion (Diagnostic yields of CMA testing; page unavailable) summarizes diagnostic yields from earlier studies, but gives no OR of 4.96 or analysis using their small control groups. Searches for the OR and the stated meta-analysis found no supporting passage in our copy. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
    • cites [7] source
    • cites [8] source
  • Classified as probably not a substantial claim. 11
  • May combine two claims. 10

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The 15q11.2 deletion is associated with congenital heart disease.

    “The deletion has also been associated with congenital heart disease (CHD).6–8”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [6] Geng J , Picker J , Zheng Z , Zhang X , Wang J , Hisama F , Brown DW , Mullen MP , Harris D , Stoler J , Seman A , Miller DT , Fu Q , Roberts AE , Shen Y . Chromosome microarray testing for patients with congenital heart defects reveals novel disease causing loci and high diagnostic yield. BMC Genomics 2014;15.doi:10.1186/1471-2164-15-1127 source
    • cites [7] source
    • cites [8] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Statistical heterogeneity between studies was assessed with the Q (χ2) test and I2 statistic.

    “We assessed statistical heterogeneity between studies with the Q (χ2) test and I2 statistic (total heterogeneity/total variability).36”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    This may lead to reassessment of the effect size of CYFIP1, which has been proposed as a large effect size neurodevelopmental gene.

    “This may lead to reassessment of the effect size of CYPFIP1, which has been proposed as a large effect size neurodevelopmental gene.12 13”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [12] source

      The Introduction and the Results section ‘CYFIP1 Interactome Is Linked to Human Disease’ link CYFIP1 to intellectual disability, autism and schizophrenia. Neither passage describes CYFIP1 as a large-effect gene or estimates its effect size. The proposed reassessment is the citing authors’ own inference, not a finding attributed to this source. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [13] source

      The Discussion (page unavailable) describes CYFIP1 as having an important role in neurodevelopmental disease and reports pathological effects of increased dosage. It does not characterize CYFIP1 as a large-effect-size gene or estimate its effect size. The proposed reassessment is the citing authors’ own inference, not a finding attributed to this source. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Generalised seizures predominate in deletion probands (6.4%, 21/326) and duplication probands (5.7%, 10/76).

    “A broad spectrum ranging from (benign) focal epilepsies to severe syndromic epilepsies is reported in deletion and duplication-carrying probands, with a predominance of generalised seizures in both deletion (6.4%, 21/326)) and duplication probands (5.7%, 10/76)).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The mean number of genes, mean pLI score and median size of additional pathogenic autosomal CNVs are similar in deletion and duplication proband carriers.

    “The mean number of genes, the mean pLI score and the median size of additional pathogenic autosomal CNVs are also similar in deletion and duplication proband carriers (online supplementary figures S4A-C).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    The estimated frequency of epilepsy in 15q11.2 deletion carriers is 3.5% or 2.1% depending on control group.

    “Based on the prevalence of epilepsy in the paediatric population of 6.8 per 1000 children,39 we estimate the frequency of epilepsy in deletion carriers at 3.5% or 2.1% (table 4).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] source

  • May combine two claims.

    Findingown data

    The effect size of the 15q11.2 deletion on general intelligence is a decrease of 4.3 IQ points, equivalent to a shift of 0.28 z-scores.

    “The effect size of the 15q11.2 on general intelligence is very mild with a decrease of 4.3 points in IQ, which is equivalent to a shift in IQ of 0.28 z-scores.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The distribution of epilepsy types is similar in 15q11.2 deletion and duplication carriers, with generalised seizures in 6.4% and 5.7%, respectively.

    “Even the distribution of epilepsy types was similar in deletion and duplication carriers (generalised seizures in 6.4%–5.7%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the SJCHU database, among 406 CNVs with a pLI between 0.5 and 3, 60.6% are classified as benign, 7.6% as unknown, and 31.8% as pathogenic.

    “In the SJCHU database, the diagnostic classification of 406 CNVs with a pLI between 0.5 and 3 is benign for 60.6% (n=246), unknown for 7.6% (n=31) and pathogenic for 31.8% (n=129) (online supplementary figure S5).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Publication bias was evaluated with contour-enhanced funnel plots and Egger's test.

    “Publication bias was evaluated with the contour-enhanced funnel plot with reference line in zero (online supplementary figures S2 and S3). Funnel plot asymmetry was evaluated with a regression test (Egger’s test).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The meta-analyses used a random-effects model.

    “We fitted a random-effects model to the data used.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    If the 15q11.2 deletion had been less frequent, it would not have been identified as a neurodevelopmental risk factor.

    “If the 15q11.2 deletion had been less frequent, it would obviously not have been identified as a neurodevelopmental risk factor.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Many early case-control studies grossly underestimated the frequency of the deletion in the general population due to very small control groups.

    “However, many of the early case–control studies grossly underestimated the frequency of the deletion in the general population due to very small control groups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    It is unclear which features among cognitive symptoms, seizure, and heart malformations mainly drive enrichment in neurodevelopmental cohorts.

    “For example, it is unclear, which features among cognitive symptoms, seizure and heart malformations are mainly driving enrichment in neurodevelopmental cohorts.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The association of the 15q11.2 deletion with ASD and CHD has yet to be demonstrated.

    “This suggests that clinical series will report similar frequencies regardless of any formal association (ie, association of the 15q11.2 deletion with ASD and CHD has yet to be demonstrated).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    There is strong evidence associating the 15q11.2 deletion with NDDs and a decrease in cognitive abilities.

    “There is strong evidence associating the 15q11.2 deletion with NDDs and a decrease in cognitive abilities so this variant should not be classified as ‘uncertain significance’.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 15q11.2 deletion has been assigned in laboratories as a variant of uncertain clinical significance, likely pathogenic, or pathogenic with variable expressivity and incomplete penetrance.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Variants with uncertain clinical significance are subcategorised into likely pathogenic, likely benign, and no subclassification.

    “Variants with uncertain clinical significance are subcategorised in likely pathogenic, likely benign and no subclassification.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [45] source
    • cites [46] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Different unselected population cohorts may provide slightly different prevalences of the 15q11.2 deletion and therefore change our estimates.

    “Different unselected population cohorts may provide slightly different prevalence’s of the 15q11.2 deletion and therefore change our estimates.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The American College of Medical Genetics guidelines recommend three categories of clinical significance: pathogenic, uncertain clinical significance, and benign.

    “The guidelines of the American College of Medical Genetics45 46 recommend three categories of clinical significance including pathogenic, uncertain clinical significance and benign.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [45] source
    • cites [46] source

  • May combine two claims.

    Interpretationreasoning

    The effect size of the 15q11.2 deletion translates into a frequency of ID of 4.0% in deletion carriers, compared with 2% in the general population.

    “This is identical to the estimate of the impact on IQ measured in carriers of the 15q11.2 deletion in the general Icelandic population41 and translates into a frequency of ID of 4.0% (compared with 2% in the general population).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The general population frequency of ID is 2%.
20 of 20

  • The authors state this as an assumption.

    Every proband with a 15q11.2 deletion or duplication carries additional pathogenic variants.

    “our working hypothesis is that every proband with a 15q11.2 deletion or duplication carry additional pathogenic variants.”

  • The authors state this as an assumption.

    An additive model applies to the translation of the IQ effect into ID risk.

    “Assuming an additive model, this effect translates into a 4% risk for ID (compared with 2% in the general population).”

  • The paper relies on this without support.

    The 15q11.2 deletion has been assigned in laboratories as a variant of uncertain clinical significance, likely pathogenic, or pathogenic with variable expressivity and incomplete penetrance.

    “The 15q11.2 deletion has been assigned in laboratories as a variant of uncertain clinical significance; likely pathogenic as well as pathogenic with variable expressivity and incomplete penetrance.”

  • The paper relies on this without support.

    The general population frequency of ID is 2%.

    “This is identical to the estimate of the impact on IQ measured in carriers of the 15q11.2 deletion in the general Icelandic population41 and translates into a frequency of ID of 4.0% (compared with 2% in the general population).”

  • The paper relies on this without support.

    The pLI sum of the 15q11.2 deletion is 1.69.

    “We investigated features of deletions with a pLI sum similar to the 15q11.2 deletion (pLI sum=1.69).”
5 of 5

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Consistentz = 2.1337reported p = .0329 · recomputed p = .033

    “(z=2.1337, p = .0329”

  • Consistentz = 3.3826reported p = .0007 · recomputed p < .001

    “(z=3.3826, p = .0007”

2 of 2

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.

  • Generalised-seizure percentage has an inconsistent denominator

    Minor

    Ten of 76 duplication probands is 13.2%, not 5.7%. The reported percentage corresponds approximately to ten of the 176 duplication probands described elsewhere.

    Reported 5.7 · recomputed 13.157895

  • Duplication proband percentages use the wrong denominator

    Minor

    Among 170 duplication probands, 152 children constitute 89.4%, not 86.4%. The stated 86.4% uses 176, the total number of duplication probands, rather than the 170 with age data.

    Reported 86.4 · recomputed 89.411765

  • Discussion gives a different autism frequency for duplication probands

    Minor

    The discussion assigns approximately 17% autism frequency to the duplication-based control group, whereas table 4 reports 13.6% for duplication probands.

  • Stated BP1-BP2 span conflicts with its coordinates

    Minor

    The stated coordinates span 0.2 Mb, or 200 kb, rather than approximately 500 kb.

4 of 4

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Jønch, A. E., Douard, E., Moreau, C., Van Dijck, A., Passeggeri, M., Kooy, F., Puechberty, J., Campbell, C., Sanlaville, D., Lefroy, H., Richetin, S., Pain, A., Geneviève, D., Kini, U., Le Caignec, C., Lespinasse, J., Skytte, A.-B., Isidor, B., Zweier, C., Caberg, J.-H., Delrue, M.-A., Møller, R. S., Bojesen, A., Hjalgrim, H., Brasch-Andersen, C., Lemyre, E., Ousager, L. B., & Jacquemont, S.
Affiliations
  • University of Southern Denmark (DK)
  • Centre Hospitalier Universitaire Sainte-Justine (CA)
  • Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
  • Centre Hospitalier Universitaire Vaudois (CH)
  • Hôpital Arnaud de Villeneuve (FR)
  • University of Oxford (GB)
  • Centre National de la Recherche Scientifique (FR)
  • Service of Medical Genetics, CHUV Lausanne, Lausanne, Switzerland
  • Inserm (FR)
  • John Radcliffe Hospital (GB)
  • Service de Génétique Médical, CHU Nantes, Nantes, France
  • Service de Cytogenetique, Centre Hospitalier de Chambéry, Chambéry, France
  • Aarhus University (DK)
  • Centre Hospitalier Universitaire de Nantes (FR)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Centre Hospitalier Universitaire de Liège (BE)
  • Filadelfia (DK)
  • Vejle Sygehus (DK)
  • Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
Corresponding author
Jacquemont, Sébastien
ORCID
Venue
Journal of Medical Genetics
Publisher
BMJ
Published
2019-08-26
Volume
56
Issue
10
Pages
701-710
ISSN
  • 0022-2593 (ISSN-L)
  • 1468-6244
DOI
10.1136/jmedgenet-2018-105879
PMC
PMC6817694
OpenAlex
W2970512107
Semantic Scholar
f3a51b262a7a55d485c2435e1153907795c98ca1
Cited by
75
References
47
Citations by year
2026: 8 · 2025: 10 · 2024: 18 · 2023: 5 · 2022: 15 · 2021: 13 · 2020: 6
FWCI
4.73
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Journal of Medical Genetics (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, cc-by-nc)
  • HAL (submittedVersion, cc-by-nc)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc)
  • PubMed Central (submittedVersion, cc-by-nc)
  • IRIS (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
  • Open Repository and Bibliography (University of Liège) (submittedVersion, cc-by-nc)
Funders
  • SJ holds a Bursary Professor Fellowship from the Swiss National Science Foundation
  • The Region of Zealand and Region of Southern of Denmark Joint Research Fund (14-001308)
  • SJ holds a Canada Research Chair in neurodevelopmental disorders
  • Odense University Hospital Free Research Fund (No.15-A857)
  • SJ holds a Chair at the Jeanne et Jean Louis Lévesque Foundation
  • Ph.D. Scholarship from the Region of Southern of Denmark
  • Ph.D. Scholarship from the Faculty of Health Sciences, University of Southern of Denmark
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
neurodevelopmental disorders, effect size, intellectual disability, schizophrenia, epilepsy, IQ, autism spectrum disorder, cardiac anomalies, ascertainment bias, genetic counseling, prenatal diagnosis, phenotypic variability
MeSH terms
Loss of Function Mutation, Autistic Disorder, Epilepsy, Female, Heart Diseases, Humans, Male, Intellectual Disability, Cohort Studies, Case-Control Studies, Sequence Deletion, DNA Copy Number Variations, Neurodevelopmental Disorders

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-27.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-27.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review