Journal
AMERICAN JOURNAL OF PSYCHIATRY
Volume 179, Issue 3, Pages 216-225Publisher
AMER PSYCHIATRIC PUBLISHING, INC
DOI: 10.1176/appi.ajp.2021.21010101
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Funding
- Friedman Brain Institute
- Beatrice and Samuel A. Seaver Foundation
- Stanley Center for Psychiatric Research
- NIMH [R01MH120170, R01MH119084, U01 MH109528, R01MH124679, R37MH057881, R01MH110427]
- Swedish Research Council [2015-02271, 2018-02487, 2018-05973, sens2018605]
- CIMED
- Region Stockholm
- Anorexia Nervosa Genetics Initiative (ANGI), an initiative of the Klarman Family Foundation
- Swedish Research Council (Vetenskapsradet) [538-2013-8864]
- Brain and Behavior Research Foundation Distinguished Investigator Grant
- Lundbeck Foundation [R276-2018-4581]
- Swedish Research Council
- Torsten and Ragnar Soderbergs Foundation
- Karolinska Institutet
- Stockholm County Council
- AFA Insurance
- Lundbeckfonden
- Shire
- Mindworks Charitable Lead Trust
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This study estimated the heritability of OCD using two homogeneous cohorts and found that common inherited risk variation accounted for most of the heritable variation in OCD. Contrary to previous studies, SNPs with low MAF also made meaningful contributions to the heritability of OCD. These results support the expectation of the polygenic model for OCD inheritance.
Objective: Obsessive-compulsive disorder (OCD) is known to be substantially heritable; however, the contribution of genetic variation across the allele frequency spectrum to this heritability remains uncertain. The authors used two new homogeneous cohorts to estimate the heritability of OCD from inherited genetic variation and contrasted the results with those of previous studies. Methods: The sample consisted of 2,090 Swedish-born individuals diagnosed with OCD and 4,567 control subjects, all genotyped for common genetic variants, specifically .400,000 single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) >_0.01. Using genotypes of these SNPs to estimate distant familial relationships among individuals, the authors estimated the heritability of OCD, both overall and partitioned according to MAF bins. Results: Narrow-sense heritability of OCD was estimated at 29% (SE5 4%). The estimate was robust, varying only modestly under different models. Contrary to an earlier study, however, SNPs with MAF between 0.01 and 0.05 accounted for 10% of heritability, and estimated heritability per MAF bin roughly followed expectations based on a simple model for SNP-based heritability. Conclusions: These results indicate that common inherited risk variation (MAF >_0.01) accounts for most of the heritable variation in OCD. SNPs with low MAF contribute meaningfully to the heritability of OCD, and the results are consistent with expectation under the infinitesimal model (also referred to as the polygenic model), where risk is influenced by a large number of loci across the genome and across MAF bins.
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