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The dopamine receptor 2 (DRD2), encoded by the<jats:italic>DRD2<\/jats:italic>gene, has been shown to mediate dopamine\u2019s inhibition of GnRH neuron excitability through pre- and post-synaptic interactions in murine models. Further, DRD2 is known to mediate prolactin (PRL) inhibition by dopamine, and high blood level of PRL have been found in more than one third of women with PCOS. We recently identified<jats:italic>PRL<\/jats:italic>as a gene contributing to PCOS risk and reported<jats:italic>DRD2<\/jats:italic>conferring risk for type 2 diabetes and depression, which can both coexist with PCOS. Given DRD2 mediating dopamine\u2019s action on neuroendocrine profiles and association with metabolic-mental states related to PCOS, polymorphisms in<jats:italic>DRD2<\/jats:italic>may predispose to development of PCOS. Therefore, we aimed to investigate whether<jats:italic>DRD2<\/jats:italic>variants are in linkage to and\/or linkage disequilibrium (i.e., linkage and association) with PCOS in Italian families. In 212 Italian families, we tested 22 variants within the<jats:italic>DRD2<\/jats:italic>gene for linkage and linkage disequilibrium with PCOS. We identified five novel variants significantly linked to the risk of PCOS. This is the first study to identify<jats:italic>DRD2<\/jats:italic>as a risk gene in PCOS, however, functional studies are needed to confirm these results.<\/jats:p>","DOI":"10.1186\/s13048-023-01205-2","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T16:01:54Z","timestamp":1691683314000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Linkage and association of variants in the dopamine receptor 2 gene (DRD2) with polycystic ovary syndrome"],"prefix":"10.1186","volume":"16","author":[{"given":"Mutaz","family":"Amin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Horst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Gragnoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"issue":"6","key":"1205_CR1","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1210\/jc.2003-032046","volume":"89","author":"R Azziz","year":"2004","unstructured":"Azziz R, et al. 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The Bios Ethical Committee approved this study (Prot.PR\/Mg\/Cg\/311708).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"C.G. is Professor of Medicine and Chief of Endocrinology and Endowed Puller Chair at Creighton University School of Medicine, Omaha, NE, and Adjunct Professor of Public Health Sciences, Penn State University College of Medicine, Hershey, PA; N.H. is a medical student at Creighton University School of Medicine, Omaha, NE; M.A. has an MD and a PhD in Genetics (University of Paris) and is a geneticist at Orphanet | INSERM-US14, Paris, France, and member of the executive committee, European Reference Network for the Intellectual Disabilities (ERN-ITHACA) and the International Consortium of Gene Curation Coalition (GenCC).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 information"}},{"value":"The authors have declared that they have no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"158"}}