The Genetic Architecture of Obsessive-Compulsive Disorder: Contribution of Liability to OCD From Alleles Across the Frequency Spectrum

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 gene...

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Veröffentlicht in:	The American journal of psychiatry Jg. 179; H. 3; S. 216
Hauptverfasser:	Mahjani, Behrang, Klei, Lambertus, Mattheisen, Manuel, Halvorsen, Matthew W, Reichenberg, Abraham, Roeder, Kathryn, Pedersen, Nancy L, Boberg, Julia, de Schipper, Elles, Bulik, Cynthia M, Landén, Mikael, Fundín, Bengt, Mataix-Cols, David, Sandin, Sven, Hultman, Christina M, Crowley, James J, Buxbaum, Joseph D, Rück, Christian, Devlin, Bernie, Grice, Dorothy E
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.03.2022
Schlagworte:	Alleles Genome-Wide Association Study - methods Humans Multifactorial Inheritance Obsessive-Compulsive Disorder - diagnosis Obsessive-Compulsive Disorder - genetics Polymorphism, Single Nucleotide - genetics Obsessive-Compulsive Disorder Genetics Heritability
ISSN:	1535-7228, 1535-7228
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Zusammenfassung:	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. 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. Narrow-sense heritability of OCD was estimated at 29% (SE=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. 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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1535-7228 1535-7228
DOI:	10.1176/appi.ajp.2021.21010101