{"doi":"10.1101/2021.01.26.21250409","title":"The genetic architecture of obsessive-compulsive disorder: alleles across the frequency spectrum contribute liability to OCD","abstract":"<jats:title>Abstract</jats:title>\n                <jats:sec>\n                  <jats:title>Objective</jats:title>\n                  <jats:p>Obsessive-compulsive disorder (OCD) is known to be substantially heritable; however, the contribution of common genetic variation across the allele frequency spectrum to this heritability remains uncertain. We use two new, homogenous cohorts to estimate heritability of OCD from common genetic variation and contrast results with prior studies.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>The sample consisted of 2096 Swedish-born individuals diagnosed with OCD and 4609 controls, all genotyped for common genetic variants, specifically &gt;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, we estimated heritability of OCD, both overall and partitioned according to MAF bins.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>We estimated narrow-sense heritability of 28% (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 8% of heritability and estimated heritability per bin roughly follows expectations based on a simple model for SNP-based heritability.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>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,” where risk is influenced by a large number of loci across the genome and across MAF bins.</jats:p>\n                </jats:sec>","journal":"medRxiv","year":null,"id":14024,"datarank":0.23262624568871965,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.024682091520736017,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.024682091520736017,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":40075,"name":"Lambertus Klei","orcid":"0000-0003-4524-4968","position":1,"is_corresponding":false},{"id":5190,"name":"Manuel Mattheisen","orcid":"0000-0002-8442-493X","position":2,"is_corresponding":false},{"id":112584,"name":"Matthew W. Halvorsen","orcid":null,"position":3,"is_corresponding":false},{"id":17205,"name":"Abraham Reichenberg","orcid":"0000-0003-2729-8575","position":4,"is_corresponding":false},{"id":40174,"name":"Kathryn Roeder","orcid":"0000-0002-8869-6254","position":5,"is_corresponding":false},{"id":5347,"name":"Nancy L. Pedersen","orcid":"0000-0001-8057-3543","position":6,"is_corresponding":false},{"id":112585,"name":"Julia Boberg","orcid":null,"position":7,"is_corresponding":false},{"id":112586,"name":"Elles de Schipper","orcid":null,"position":8,"is_corresponding":false},{"id":112587,"name":"Cynthia M. Bulik","orcid":"0000-0001-7772-3264","position":9,"is_corresponding":false},{"id":3818,"name":"Mikael Landén","orcid":"0000-0002-4496-6451","position":10,"is_corresponding":false},{"id":112588,"name":"Bengt Fundín","orcid":null,"position":11,"is_corresponding":false},{"id":17215,"name":"David Mataix‐Cols","orcid":"0000-0002-4545-0924","position":12,"is_corresponding":false},{"id":112589,"name":"Sven Sandin","orcid":"0000-0001-6994-4884","position":13,"is_corresponding":false},{"id":1068,"name":"Christina M. Hultman","orcid":"0000-0002-0327-2410","position":14,"is_corresponding":false},{"id":62338,"name":"James J. Crowley","orcid":"0000-0001-9051-1557","position":15,"is_corresponding":false},{"id":35461,"name":"Joseph D. Buxbaum","orcid":"0000-0001-8898-8313","position":16,"is_corresponding":false},{"id":112590,"name":"Christian Rück","orcid":null,"position":17,"is_corresponding":false},{"id":40215,"name":"Bernie Devlin","orcid":"0000-0003-2524-4290","position":18,"is_corresponding":false},{"id":112591,"name":"Dorothy E. Grice","orcid":"0000-0002-8833-2549","position":19,"is_corresponding":false},{"id":104445,"name":"Behrang Mahjani","orcid":"0000-0001-6087-9537","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21071399","pmcid":null,"openalex_id":"https://openalex.org/W3122595616","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5R01MH120170-05","title":"Eating Disorders Genetics Initiative (EDGI)"},{"funder_name":"National Institutes of Health","grant_id":"5R01MH124679-02","title":"1/2 Rare Genetic Variation and Risk for Obsessive Compulsive Disorder"},{"funder_name":"National Institutes of Health","grant_id":"5R37MH057881-25","title":"Genetics Association in Schizophrenia and Other Disorders"},{"funder_name":"National Institutes of Health","grant_id":"5R01MH110427-02","title":"OCD: Novel Comparative Genomic Approaches to Identify Disease and Treatment Mechanisms"},{"funder_name":"National Institutes of Health","grant_id":"3U01MH109528-02S1","title":"1/7 Psychiatric Genomics Consortium: Finding actionable variation"},{"funder_name":"National Institutes of Health","grant_id":"5R01MH119084-03","title":"Predicting Binge and Purge Episodes from Passive and Active Apple Watch Data Using a Dynamical Systems Approach"}],"total_grants":6,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2021,"count":2},{"year":2023,"count":1}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.medrxiv.org/content/medrxiv/early/2021/01/27/2021.01.26.21250409.full.pdf","host_type":"repository"},{"url":"https://doi.org/10.1101/2021.01.26.21250409","host_type":"GREEN"},{"url":"https://www.medrxiv.org/content/medrxiv/early/2021/01/27/2021.01.26.21250409.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2021.01.26.21250409","host_type":"publisher"},{"url":"https://dx.doi.org/10.1101/2021.01.26.21250409","host_type":""}],"fields_of_study":["Obsessive-Compulsive Spectrum Disorders","Autism Spectrum Disorder Research","Medicine","Psychology","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":[],"keywords":["Heritability","Minor allele frequency","Single-nucleotide polymorphism","Genetics","Genetic architecture","Missing heritability problem","Biology","Genetic variation","Allele frequency","Genome-wide association study","Allele","Genotype","Quantitative trait locus","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-05-31T23:21:48.999273Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}