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Given osteoarthritis (OA) is a highly polygenic disease, we set out to determine if an association exists between OA and genomic heterozygosity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>End-stage knee and hip OA patients and healthy controls were recruited from the Newfoundland and Labrador (NL) population. The Arthritis Research UK Osteoarthritis Genetics (arcOGEN) consortium database was utilized as a replication cohort. DNA was extracted from blood samples and genotyped. Individual rates of observed heterozygosity (HetRate) and heterozygosity excess (HetExcess) relative to the expected were mathematically derived, and standardized to a z-score. Logistic regression modeling was used to examine the association between OA and HetRate or HetExcess. A total of 559 knee and hip OA patients (mean age 66.5\u00a0years, body mass index (BMI) 33.7\u00a0kg\/m<jats:sup>2<\/jats:sup>, and 55% females) and 118 healthy controls (mean age 56.4\u00a0years, BMI 29.5\u00a0kg\/m<jats:sup>2<\/jats:sup>, and 59% female) were included in the NL cohort analysis. We found that OA had an inverse relationship with HetRate and HetExcess with odds ratios of 0.64 (95% CI: 0.45\u20130.91) and 0.65 (95% CI: 0.45\u20130.93) per standard deviation (SD), respectively. The arcOGEN data included 2,019 end-stage knee and hip OA patients and 2,029 healthy controls, validating our findings with HetRate and HetExcess odds ratios of 0.60 (95% CI: 0.56\u20130.64) and 0.44 (95% CI: 0.40\u20130.47) per SD, respectively.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results are the first to clearly show evidence, from two separate cohorts, that reduced genomic heterozygosity confers a risk for the future development of OA.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12864-024-10015-9","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T15:01:47Z","timestamp":1705762907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genomic heterozygosity is associated with a lower risk of osteoarthritis"],"prefix":"10.1186","volume":"25","author":[{"given":"Robert","family":"Gill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Furey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Spector","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Proton","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangju","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,20]]},"reference":[{"issue":"7","key":"10015_CR1","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1002\/art.42089","volume":"74","author":"H Long","year":"2022","unstructured":"Long H, Liu Q, Yin H, Wang K, Diao N, Zhang Y, Lin J, Guo A. 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Accessed 20 Feb 2023."}],"container-title":["BMC Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12864-024-10015-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12864-024-10015-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12864-024-10015-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T15:02:34Z","timestamp":1705762954000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgenomics.biomedcentral.com\/articles\/10.1186\/s12864-024-10015-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,20]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["10015"],"URL":"https:\/\/doi.org\/10.1186\/s12864-024-10015-9","relation":{},"ISSN":["1471-2164"],"issn-type":[{"value":"1471-2164","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,20]]},"assertion":[{"value":"22 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Both NFOAS and CODING study were approved by the Health Research Ethics Authority of Newfoundland and Labrador (HREB; NFOAS\u2014# 2011.311 & CODING\u2014#10.33). The arcOGEN was approved by the Oxfordshire Research Ethics Committee with reference 07\/H0606\/150. Written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Author P.R. discloses they are a paid consultant for AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Research support as a PI from AbbVie, Pfizer, Novartis, and Janssen. Payment or honoraria from AbbVie, BMS, Eli-Lilly, Jansen, Pfizer, Novartis, UCB. Leadership or fiduciary role in the Canadian Academy of Health Sciences and Canadian Council of Academies.Author G.Z. discloses payment or honoraria from The Canadian Rheumatology Society 2022 and 7th World Congress on Controversies, Debates & Consensus on Bone, Muscle & Joint Diseases 2019.All other authors have no financial conflict of interest to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"85"}}