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  • Mahjani, BehrangKarolinska Institutet (author)

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

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • American Psychiatric Association Publishing,2022

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/312370
  • https://gup.ub.gu.se/publication/312370URI
  • https://doi.org/10.1176/appi.ajp.2021.21010101DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:149528672URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

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  • Klei, Lambertus (author)
  • Mattheisen, ManuelKarolinska Institutet (author)
  • Halvorsen, Matthew W (author)
  • Reichenberg, Abraham (author)
  • Roeder, Kathryn (author)
  • Pedersen, Nancy LKarolinska Institutet (author)
  • Boberg, JuliaKarolinska Institutet (author)
  • de Schipper, EllesKarolinska Institutet (author)
  • Bulik, Cynthia M (author)
  • Landén, Mikael,1966Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xlandt (author)
  • Fundín, Bengt (author)
  • Mataix-Cols, DavidKarolinska Institutet (author)
  • Sandin, SvenKarolinska Institutet (author)
  • Hultman, Christina M (author)
  • Crowley, James J (author)
  • Buxbaum, Joseph D (author)
  • Rück, ChristianKarolinska Institutet (author)
  • Devlin, Bernie (author)
  • Grice, Dorothy E (author)
  • Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

Related titles

  • In:The American journal of psychiatry: American Psychiatric Association Publishing179:3, s. 216-2251535-72280002-953X

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