{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:06:11Z","timestamp":1787983571168,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010764","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["F31HD103397"],"award-info":[{"award-number":["F31HD103397"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["U54MD010722"],"award-info":[{"award-number":["U54MD010722"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["R01HG011405"],"award-info":[{"award-number":["R01HG011405"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01CA253560"],"award-info":[{"award-number":["U01CA253560"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Females with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, have an increased risk of developing cardiometabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). While only diagnosable in females, males with a family history of PCOS can also exhibit a poor cardiometabolic profile. Therefore, we aimed to elucidate the role of sex in the cardiometabolic comorbidities observed in PCOS by conducting bidirectional genetic risk score analyses in both sexes. We first conducted a phenome-wide association study (PheWAS) using PCOS polygenic risk scores (PCOS\n                    <jats:sub>PRS<\/jats:sub>\n                    ) to identify potential pleiotropic effects of PCOS\n                    <jats:sub>PRS<\/jats:sub>\n                    across 1,380 medical conditions recorded in the Vanderbilt University Medical Center electronic health record (EHR) database, in females and males. After adjusting for age and genetic ancestry, we found that European (EUR)-ancestry males with higher PCOS\n                    <jats:sub>PRS<\/jats:sub>\n                    were significantly more likely to develop hypertensive diseases than females at the same level of genetic risk. We performed the same analysis in an African (AFR)-ancestry population, but observed no significant associations, likely due to poor trans-ancestry performance of the PRS. Based on observed significant associations in the EUR-ancestry population, we then tested whether the PRS for comorbid conditions (e.g., T2D, body mass index (BMI), hypertension, etc.) also increased the odds of a PCOS diagnosis. Only BMI\n                    <jats:sub>PRS<\/jats:sub>\n                    and T2D\n                    <jats:sub>PRS<\/jats:sub>\n                    were significantly associated with a PCOS diagnosis in EUR-ancestry females. We then further adjusted the T2D\n                    <jats:sub>PRS<\/jats:sub>\n                    for measured BMI and BMI\n                    <jats:sub>residual<\/jats:sub>\n                    (regressed on the BMI\n                    <jats:sub>PRS<\/jats:sub>\n                    and enriched for the environmental contribution to BMI). Results demonstrated that genetically regulated BMI primarily accounted for the relationship between T2D\n                    <jats:sub>PRS<\/jats:sub>\n                    and PCOS. Overall, our findings show that the genetic architecture of PCOS has distinct sex differences in associations with genetically correlated cardiometabolic traits. It is possible that the cardiometabolic comorbidities observed in PCOS are primarily explained by their shared genetic risk factors, which can be further influenced by biological variables including sex and BMI.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1010764","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T14:09:37Z","timestamp":1685542177000},"page":"e1010764","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sex modifies the effect of genetic risk scores for polycystic ovary syndrome on metabolic phenotypes"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1591-6914","authenticated-orcid":true,"given":"Ky\u2019Era V.","family":"Actkins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Jean-Pierre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-8448","authenticated-orcid":true,"given":"Melinda C.","family":"Aldrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Digna R.","family":"Velez Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5143-2282","authenticated-orcid":true,"given":"Lea K.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"pgen.1010764.ref001","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/humrep\/deh098","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).","volume":"19","author":"Rotterdam ESHRE\/ASRM-Sponsored PCOS consensus workshop group","year":"2004","journal-title":"Hum Reprod"},{"key":"pgen.1010764.ref002","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1093\/humrep\/dey256","article-title":"Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"33","author":"HJ Teede","year":"2018","journal-title":"Hum 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