Revealing the complex genetic architecture of obsessive–compulsive disorder using meta-analysis
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Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P-values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 (P=7.1 × 10-7; odds ratio (OR)=1.21; confidence interval (CI): 1.12-1.31, CASC8/CASC11), rs1030757 (P=1.1 × 10-6; OR=1.18; CI: 1.10-1.26, GRID2) and rs12504244 (P=1.6 × 10-6; OR=1.18; CI: 1.11-1.27, KIT). Variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2 and CDH20, identified in linkage peaks and the original GWASs, were among the top signals. Polygenic risk scores for each individual study predicted case-control status in the other by explaining 0.9% (P=0.003) and 0.3% (P=0.0009) of the phenotypic variance in OCGAS and the European IOCDF-GC target samples, respectively. The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e.=0.04). Strikingly, ∼65% of the SNP-based heritability in the OCGAS sample was accounted for by SNPs with minor allele frequencies of ⩾40%. This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.
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The common single nucleotide polymorphism heritability of OCD is estimated at 28% in meta-analyses, while overall heritability is reported at 40% to 50%.
“The common single nucleotide polymorphism heritability of OCD has been estimated to be 28% in meta-analyses (18), whereas the overall heritability is reported to be 40% to 50% (19–24).”
From Maternal Effects as Causes of Risk for Obsessive-Compulsive Disorder (2020) · cites this paper as [18]
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Comparison of neurocognitive performance in familial versus sporadic obsessive-compulsive disorder
Bhattacharya, M., Balachander, S., Viswanath, B., & Reddy, Y. C. J. (2021) · Journal of Obsessive-Compulsive and Related Disorders · doi:10.1016/j.jocrd.2021.100666 · Cited by 5 · see citing works
- Authors
- International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
- Venue
- Molecular Psychiatry
- Published
- 2017-08-01
- Volume
- 23
- Issue
- 5
- Pages
- 1181-1188
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC6660151
- OpenAlex
- W2739834351
- Cited by
- 618
- References
- 48
- Citations by year
- 2026: 60 · 2025: 88 · 2024: 102 · 2023: 84 · 2022: 77 · 2021: 83 · 2020: 48 · 2019: 52 · 2018: 21 · 2017: 2
- FWCI
- 41.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- U.S. Department of Health and Human Services
- International OCD Foundation
- National Institutes of Health
- National Institute of Mental Health (MH079494, ZIAMH002930, K23MH085057, R01MH071507, MH079488, R21MH087748, R13MH073250, MH071507, MH079487, MH079489, U01MH109536, R01MH079489, R01MH079487, MH002930-06, MH002930, R01MH079488, R01MH079494, T32MH014592)
- National Institute of Neurological Disorders and Stroke (U01NS040024, R01NS040024)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- obsessive-compulsive disorder, genetic architecture, polygenic risk score, GRID2, KIT
- MeSH terms
- Alleles, Female, Gene Frequency, Humans, Genetic Linkage, Male, Neoplasm Proteins, Obsessive-Compulsive Disorder, Case-Control Studies, Receptors, Glutamate, Genetic Predisposition to Disease, Multifactorial Inheritance, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study, RNA, Long Noncoding
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