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It is characterized by anovulation and irregular menses and is associated with type 2 diabetes. Neuroendocrine pathways and ovarian and adrenal dysfunctions are possibly implicated in the disorder pathogenesis. The melatonin system plays a role in PCOS. Melatonin receptors are expressed on the surface of ovarian granulosa cells, and variations in the melatonin receptor genes have been associated with increased risk of PCOS in both familial and sporadic cases. We have recently reported the association of variants in <jats:italic>MTNR1A<\/jats:italic> and <jats:italic>MTNR1B<\/jats:italic> genes with familial type 2 diabetes. In this study, we aimed to investigate whether <jats:italic>MTNR1A<\/jats:italic> and <jats:italic>MTNR1B<\/jats:italic> contribute to PCOS risk in peninsular families. In 212 Italian families phenotyped for PCOS, we amplified by microarray 14 variants in the <jats:italic>MTNR1A<\/jats:italic> gene and 6 variants in the <jats:italic>MTNR1B<\/jats:italic> gene and tested them for linkage and linkage disequilibrium with PCOS. We detected 4 variants in the <jats:italic>MTNR1A<\/jats:italic> gene and 2 variants in the <jats:italic>MTNR1B<\/jats:italic> gene significantly linked and\/or in linkage disequilibrium with the risk of PCOS (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). All variants are novel and have not been reported before with PCOS or any of its related phenotypes, except for 3 variants previously reported by us to confer risk for type 2 diabetes and 1 variant for type 2 diabetes-depression comorbidity. These findings implicate novel melatonin receptor genes\u2019 variants in the risk of PCOS with potential functional roles.<\/jats:p>","DOI":"10.1186\/s13048-024-01343-1","type":"journal-article","created":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T03:02:45Z","timestamp":1705114965000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The melatonin receptor genes are linked and associated with the risk of polycystic ovary syndrome"],"prefix":"10.1186","volume":"17","author":[{"given":"Teodor T.","family":"Postolache","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qamar M.","family":"Al Tinawi","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":[[2024,1,13]]},"reference":[{"issue":"5","key":"1343_CR1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.3109\/07420529209064550","volume":"9","author":"AJ Lewy","year":"1992","unstructured":"Lewy AJ, et al. 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The Bios Ethical Committee approved this study (Prot.PR\/Mg\/Cg\/311,708).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"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; Q.M.A.T. is an internal medicine resident at Creighton University School of Medicine, Omaha, NE. T.T.P. is a Professor of Psychiatry at the University of Maryland School of Medicine, Baltimore, MD, and a research investigator with the Rocky Mountain MIRECC, Aurora, CO, and the VISN 5 MIRECC, Baltimore, MD.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 information"}}],"article-number":"17"}}