{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:03:35Z","timestamp":1789718615602,"version":"4.0.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,3,7]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cardiometabolic diseases are highly comorbid, but their relationship with female\u2010specific or overwhelmingly female\u2010predominant health conditions (breast cancer, endometriosis, pregnancy complications) is understudied. This study aimed to estimate the cross\u2010trait genetic overlap and influence of genetic burden of cardiometabolic traits on health conditions unique to women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Using electronic health record data from 71\u2009008 ancestrally diverse women, we examined relationships between 23 obstetrical\/gynecological conditions and 4 cardiometabolic phenotypes (body mass index, coronary artery disease, type 2 diabetes, and hypertension) by performing 4 analyses: (1) cross\u2010trait genetic correlation analyses to compare genetic architecture, (2) polygenic risk score\u2013based association tests to characterize shared genetic effects on disease risk, (3) Mendelian randomization for significant associations to assess cross\u2010trait causal relationships, and (4) chronology analyses to visualize the timeline of events unique to groups of women with high and low genetic burden for cardiometabolic traits and highlight the disease prevalence in risk groups by age. We observed 27 significant associations between cardiometabolic polygenic scores and obstetrical\/gynecological conditions (body mass index and endometrial cancer, body mass index and polycystic ovarian syndrome, type 2 diabetes and gestational diabetes, type 2 diabetes and polycystic ovarian syndrome). Mendelian randomization analysis provided additional evidence of independent causal effects. We also identified an inverse association between coronary artery disease and breast cancer. High cardiometabolic polygenic scores were associated with early development of polycystic ovarian syndrome and gestational hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">We conclude that polygenic susceptibility to cardiometabolic traits is associated with elevated risk of certain female\u2010specific health conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.121.026561","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T05:16:44Z","timestamp":1677475004000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Inference of Causal Relationships Between Genetic Risk Factors for Cardiometabolic Phenotypes and Female\u2010Specific Health 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