The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Cognitive Performance Among Carriers of Pathogenic Copy Number Variants: Analysis of 152,000 UK Biobank Subjects
Open accessAbstract
Background The UK Biobank is a unique resource for biomedical research, with extensive phenotypic and genetic data on half a million adults from the general population. We aimed to examine the effect of neurodevelopmental copy number variants (CNVs) on the cognitive performance of participants.Methods We used Affymetrix Power Tools and PennCNV-Affy software to analyze Affymetrix microarrays of the first 152,728 genotyped individuals. We annotated a list of 93 CNVs and compared their frequencies with control datasets. We analyzed the performance on seven cognitive tests of carriers of 12 CNVs associated with schizophrenia (n = 1087) and of carriers of another 41 neurodevelopmental CNVs (n = 484).Results The frequencies of the 93 CNVs in the Biobank subjects were remarkably similar to those among 26,628 control subjects from other datasets. Carriers of schizophrenia-associated CNVs and of the group of 41 other neurodevelopmental CNVs had impaired performance on the cognitive tests, with nine of 14 comparisons remaining statistically significant after correction for multiple testing. They also had lower educational and occupational attainment (p values between 10-7 and 10-18). The deficits in cognitive performance were modest (Z score reductions between 0.01 and 0.51), compared with individuals with schizophrenia in the Biobank (Z score reductions between 0.35 and 0.90).Conclusions This is the largest study on the cognitive phenotypes of CNVs to date. Adult carriers of neurodevelopmental CNVs from the general population have significant cognitive deficits. The UK Biobank will allow unprecedented opportunities for analysis of further phenotypic consequences of CNVs.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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).”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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).”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“We used data on CNV frequency from the UK BIOBANK (151 619 individuals),16 which is an unselected population.”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [16]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The reciprocal duplication is not enriched in both the SJCHU and OUH cohorts (table 2) when using the prevalence in an unselected population provided by the UK BIOBANK (0.5%, 762/151619)16 and is therefore used as a control neutral CNV throughout the rest of this study.”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“The reciprocal duplication is not enriched in both the SJCHU and OUH cohorts (table 2) when using the prevalence in an unselected population provided by the UK BIOBANK (0.5%, 762/151619)16 and is therefore used as a control neutral CNV throughout the rest of this study.”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [16]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“There is, however, no significant enrichment 1.55 (95% CI 0.97 to 2.48) if the UK BIOBANK population frequency of 0.36% is used as the control group.”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [16]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Currently, the best estimates range from 0.36% (UK BIOBANK)16 to 0.24% (Icelandic population).41”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [16]
Experimental — accuracy not yet measuredIn the citing paper
“penetrance can be highly variable, ranging from subtle effects detectable by neuropsychological tests to mild degrees of anxiety/ADHD to co-occurrence of severe psychiatric disorders (Kendall et al., 2017; Stefansson et al., 2014; Ulfarsson et al., 2017)”
From Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders (2019) · cites this paper as Kendall et al., 2017
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality
McGrath, J., Saha, S., Chant, D., & Welham, J. (2008) · Epidemiologic Reviews · doi:10.1093/epirev/mxn001 · Cited by 2,280
Structural variation in the human genome
Feuk, L., Carson, A. R., & Scherer, S. W. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1767 · Cited by 2,111
Wang, K., Li, M., Hadley, D., Liu, R., Glessner, J., Grant, S. F. A., Hakonarson, H., & Bucan, M. (2007) · Genome Research · doi:10.1101/gr.6861907 · Cited by 1,792
Rare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475
What makes UK Biobank special?
Collins, R. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60404-8 · Cited by 1,128
Intelligence and socioeconomic success: A meta-analytic review of longitudinal research
Strenze, T. (2006) · Intelligence · doi:10.1016/j.intell.2006.09.004 · Cited by 1,019
Standard occupational classification
Surveys (1990) · HMSO eBooks · Cited by 963
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×
“Much less is known about the effects of these CNVs in adults from the general population (9, 10).”
InfluentialSelf-citationCoe, B. P., Witherspoon, K., Rosenfeld, J. A., van Bon, B. W. M., Vulto-van Silfhout, A. T., Bosco, P., Friend, K. L., Baker, C., Buono, S., Vissers, L. E. L. M., et al. (2014) · Nature Genetics · doi:10.1038/ng.3092 · Cited by 720
Microduplications 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
Self-citationCNVs conferring risk of autism or schizophrenia affect cognition in controls
Stefansson, H., Meyer-Lindenberg, A., Steinberg, S., Magnusdottir, B., Morgen, K., Arnarsdottir, S., Bjornsdottir, G., Walters, G. B., Jonsdottir, G. A., Doyle, O. M., et al. (2014) · Nature · doi:10.1038/nature12818 · Cited by 699
Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus
Jacquemont, S., Reymond, A., Zufferey, F., Harewood, L., Walters, R. G., Kutalik, Z., Martinet, D., Shen, Y., Valsesia, A., Beckmann, N. D., et al. (2011) · Nature · doi:10.1038/nature10406 · Cited by 462
Analysis of copy number variations at 15 schizophrenia-associated loci
Rees, E., Walters, J. T. R., Georgieva, L., Isles, A. R., Chambert, K. D., Richards, A. L., Mahoney-Davies, G., Legge, S. E., Moran, J. L., McCarroll, S. A., et al. (2014) · British Journal of Psychiatry · doi:10.1192/bjp.bp.113.131052 · Cited by 443
Self-citationLevinson, 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
MOLECULAR MECHANISMS FOR CONSTITUTIONAL CHROMOSOMAL REARRANGEMENTS IN HUMANS
Shaffer, L. G., & Lupski, J. R. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.297 · Cited by 418
Wain, L. V., Shrine, N. R. G., Miller, S., Jackson, V. E., Ntalla, I., Artigas, M. S., Billington, C. K., Kheirallah, A. K., Allen, R. J., Cook, J. P., et al. (2015) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00283-0 · Cited by 393
The Penetrance of Copy Number Variations for Schizophrenia and Developmental Delay
Kirov, G., Rees, E., Walters, J. T. R., Escott-Price, V., Georgieva, L., Richards, A. L., Chambert, K. D., Davies, G., Legge, S. E., Moran, J. L., et al. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.022 · Cited by 368
Self-citationThe Role of General Cognitive Ability and Job Performance: Why There Cannot Be a Debate
Schmidt, F. L. (2002) · Psychology Press eBooks · doi:10.1080/08959285.2002.9668091 · Cited by 361
Developmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence
Moreno-De-Luca, A., Myers, S. M., Challman, T. D., Moreno-De-Luca, D., Evans, D. W., & Ledbetter, D. H. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70011-5 · Cited by 330
Chance, P. F., Abbas, N., Lensch, M. W., Pentao, L., Roa, B. B., Patel, P. I., & Lupski, J. R. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.2.223 · Cited by 311
Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A
Lupski, J. R., Wise, C. A., Kuwano, A., Pentao, L., Parke, J. T., Glaze, D. G., Ledbetter, D. H., Greenberg, F., & Patel, P. I. (1992) · Nature Genetics · doi:10.1038/ng0492-29 · Cited by 281
Copy Number Variations and Cognitive Phenotypes in Unselected Populations
Männik, K., Mägi, R., Macé, A., Cole, B., Guyatt, A. L., Shihab, H. A., Maillard, A. M., Alavere, H., Kolk, A., Reigo, A., et al. (2015) · JAMA · doi:10.1001/jama.2015.4845 · Cited by 205
The clinical context of copy number variation in the human genome
Lee, C., & Scherer, S. W. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399410001390 · Cited by 188
Analysis of Intellectual Disability Copy Number Variants for Association With Schizophrenia
Rees, E., Kendall, K., Pardiñas, A. F., Legge, S. E., Pocklington, A., Escott-Price, V., MacCabe, J. H., Collier, D. A., Holmans, P., O’Donovan, M. C., et al. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.1831 · Cited by 162
Self-citationCNVs in neuropsychiatric disorders
Kirov, G. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv253 · Cited by 159
Self-citationDittwald, P., Gambin, T., Szafrański, P., Li, J., Amato, S., Divon, M. Y., Rojas, L. X. R., Elton, L., Scott, D. A., Schaaf, C. P., et al. (2013) · Genome Research · doi:10.1101/gr.152454.112 · Cited by 131
Rees, E., Walters, J., Chambert, K., O'Dushlaine, C., Szatkiewicz, J., Richards, A. L., Georgieva, L., Mahoney‐Davies, G., Legge, S. E., Moran, J. L., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt540 · Cited by 131
Self-citationCopy Number Variation in Schizophrenia in the Japanese Population
Ikeda, M., Aleksić, B., Kirov, G., Kinoshita, Y., Yamanouchi, Y., Kitajima, T., Kawashima, K., Okochi, T., Kishi, T., Zaharieva, I. T., et al. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.034 · Cited by 109
Self-citationLal, D., Ruppert, A., Trucks, H., Schulz, H., de Kovel, C. G. F., Trenité, D. G. A. K.-N., Sonsma, A. C. M., Koeleman, B. P. C., Lindhout, D., Weber, Y. G., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005226 · Cited by 101
Enhancing the Feasibility of Large Cohort Studies
Manolio, T. A., & Collins, R. (2010) · JAMA · doi:10.1001/jama.2010.1686 · Cited by 97
Intelligence, Training, and Employment.
Wagner, R. K. (1997) · American Psychologist · doi:10.1037/0003-066x.52.10.1059 · Cited by 92
Reduced burden of very large and rare CNVs in bipolar affective disorder
Grozeva, D., Kirov, G., Conrad, D. F., Barnes, C. P., Hurles, M. E., Owen, M. J., O’Donovan, M. C., & Craddock, N. J. (2013) · Bipolar Disorders · doi:10.1111/bdi.12125 · Cited by 33
Self-citation
Cited by
Sorted by citations
Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders
Sullivan, P. F., & Geschwind, D. H. (2019) · Cell · doi:10.1016/j.cell.2019.01.015 · Cited by 452
Schizophrenia and the neurodevelopmental continuum:evidence from genomics
Owen, M. J., & O’Donovan, M. C. (2017) · World Psychiatry · doi:10.1002/wps.20440 · Cited by 339
Self-citationA large data resource of genomic copy number variation across neurodevelopmental disorders
Zarrei, M., Burton, C. L., Engchuan, W., Young, E. J., Higginbotham, E. J., MacDonald, J. R., Trost, B., Chan, A. J. S., Walker, S., Lamoureux, S., et al. (2019) · npj Genomic Medicine · doi:10.1038/s41525-019-0098-3 · Cited by 187
Li, Y., Sahakian, B. J., Kang, J., Langley, C., Zhang, W., Xie, C., Xiang, S., Yu, J., Cheng, W., & Feng, J. (2022) · Nature Aging · doi:10.1038/s43587-022-00210-2 · Cited by 185
Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank
Crawford, K., Bracher-Smith, M., Owen, D., Kendall, K. M., Rees, E., Pardiñas, A. F., Einon, M., Escott-Price, V., Walters, J. T. R., O’Donovan, M. C., et al. (2019) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2018-105477 · Cited by 175
Self-citation
Metadata
- Authors
- Kendall, K. M., Rees, E., Escott-Price, V., Einon, M., Thomas, R., Hewitt, J., O’Donovan, M. C., Owen, M. J., Walters, J. T. R., & Kirov, G.
- Affiliations
- Cardiff University (GB)
- University Hospital Llandough (GB)
- Corresponding author
- Kirov, George
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 82
- Issue
- 2
- Pages
- 103-110
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2513914028
- Cited by
- 226
- References
- 32
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 23 · 2023: 29 · 2022: 36 · 2021: 30 · 2020: 18 · 2019: 31 · 2018: 19 · 2017: 8
- FWCI
- 15.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion, cc-by-nc-nd)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust (201171/Z/16/Z)
- Cardiff University (MR/L010305/1, G0800509)
- Medical Research Council (MR/L023784/2, MR/P005748/1, MR/L010305/1, G0800509, MR/L023784/1, No. MR/L010305/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- copy number variation, neurodevelopmental disorders, cognitive performance, schizophrenia, educational attainment, occupational attainment, UK Biobank, cognitive impairment
- MeSH terms
- Adult, Aged, Female, United Kingdom, Humans, Male, Middle Aged, Neuropsychological Tests, Schizophrenia, Biological Specimen Banks, DNA Copy Number Variations, Cognitive Dysfunction, 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.
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
