{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T07:23:40Z","timestamp":1782545020596,"version":"3.54.5"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:00Z","timestamp":1701734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>To assess the relationship of genetically predicted sexual behavior (age at first sex (AFS) and the number of sexual partners (NSP)) on cardiovascular diseases (CVDs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We performed two-sample Mendelian randomization (MR) with publicly available datasets from the UK Biobank and FinnGen Study, and analyzed genome-wide association results for sexual behaviors and twelve types of CVDs. The univariable MR method provided a total effect of AFS and NSP on CVDs, and showed evidence that early AFS rather than NSP was associated with CVDs, including angina pectoris (AP), atrial fibrillation and flutter (AFF), coronary atherosclerosis (CAS), deep vein thrombosis of the lower extremity (DVT-LE), heart failure (HF), hypertension (HTN), ischaemic stroke (IS), and myocardial infarction (MI). Given sex as a social determinant of CVD risk, we used gender-stratified SNPs to investigate gender differences in the development of CVDs. These results showed a stronger causal relationship of AFS on CVDs in females than in males. Further multivariable MR analyses indicated a direct effect after accounting for insomnia, number of days of vigorous physical activity 10\u2009+\u2009minutes (VPA 10\u2009+\u2009min), and time spent watching television (TV). Two-step MR demonstrated these three risk factors act as a mediator in AFS associated AP\/HTN\/HF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We provide evidence that early AFS increased the risk of CVDs. These associations may be partly caused by VPA 10\u2009+\u2009min, insomnia, and the time spent on TV. The causality of AFS on CVDs in females was stronger than in males. Conversely, genetically predicted NSP was not associated with CVDs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1250404","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T04:21:01Z","timestamp":1701750061000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Sexual behavior and cardiovascular diseases: univariable and multivariable Mendelian randomization"],"prefix":"10.3389","volume":"10","author":[{"given":"Kejing","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongliang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyu","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoying","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renke","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hefeng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u20132019: a systematic analysis for the global burden of disease study 2019","volume":"396","year":"2020","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1161\/CIRCRESAHA.117.308903","article-title":"Reducing the global burden of cardiovascular disease, part 1: the epidemiology and risk factors","volume":"121","author":"Joseph","year":"2017","journal-title":"Circ Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/nrcardio.2017.154","article-title":"Epidemiology of cardiovascular disease in young individuals","volume":"15","author":"Andersson","year":"2018","journal-title":"Nat Rev Cardiol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1001\/jama.2011.336","article-title":"Association of episodic physical and sexual activity with triggering of acute cardiac events: systematic review and meta-analysis","volume":"305","author":"Dahabreh","year":"2011","journal-title":"JAMA"},{"key":"B6","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1136\/heart.86.4.387","article-title":"Sexual activity as a trigger of myocardial infarction. 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