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

Mahjani, Behrang (author)
Karolinska Institutet
Klei, Lambertus (author)
Mattheisen, Manuel (author)
Karolinska Institutet
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Halvorsen, Matthew W (author)
Reichenberg, Abraham (author)
Roeder, Kathryn (author)
Pedersen, Nancy L (author)
Karolinska Institutet
Boberg, Julia (author)
Karolinska Institutet
de Schipper, Elles (author)
Karolinska Institutet
Bulik, Cynthia M (author)
Landén, Mikael, 1966 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Fundín, Bengt (author)
Mataix-Cols, David (author)
Karolinska Institutet
Sandin, Sven (author)
Karolinska Institutet
Hultman, Christina M (author)
Crowley, James J (author)
Buxbaum, Joseph D (author)
Rück, Christian (author)
Karolinska Institutet
Devlin, Bernie (author)
Grice, Dorothy E (author)
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 (creator_code:org_t)
American Psychiatric Association Publishing, 2022
2022
English.
In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 179:3, s. 216-225
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  • Journal article (peer-reviewed)
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

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