Sexual behavior and cardiovascular diseases: univariable and multivariable Mendelian randomization

Kejing Zhu; Zhongliang Lin; Qinyu Luo; Zhaoying Jiang; Renke He; Haiyan Wu; Jiaen Yu; Xueying Liu; Jianzhong Sheng; Hong Zhu; Hefeng Huang

doi:10.3389/fcvm.2023.1250404

Sexual behavior and cardiovascular diseases: univariable and multivariable Mendelian randomization

Front Cardiovasc Med. 2023 Dec 5:10:1250404. doi: 10.3389/fcvm.2023.1250404. eCollection 2023.

Authors

Kejing Zhu^#^{1

2}, Zhongliang Lin^#^{1

2}, Qinyu Luo^#², Zhaoying Jiang^{1

2}, Renke He^{1

2}, Haiyan Wu², Jiaen Yu², Xueying Liu^{1

2}, Jianzhong Sheng^{1

2

3}, Hong Zhu^{3

4}, Hefeng Huang^{1

2

3

4

5

6}

Affiliations

¹ Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, China.
² Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China.
⁴ Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.
⁵ Shanghai Key Laboratory of Reproduction and Development, Shanghai, China.
⁶ State Key Laboratory of Cardiology, Shanghai, China.

^# Contributed equally.

Abstract

Background: 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).

Methods and results: 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 + minutes (VPA 10 + min), and time spent watching television (TV). Two-step MR demonstrated these three risk factors act as a mediator in AFS associated AP/HTN/HF.

Conclusions: We provide evidence that early AFS increased the risk of CVDs. These associations may be partly caused by VPA 10 + min, 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.

Keywords: Mendelian randomization; cardiovascular diseases; causal relationship; sexual behaviors; statistic method.

Grants and funding

National Key Research and Development Program of China (No. 2022YFC2703000, No. 2021YFC2700603), The National Natural Science Foundation of China (No. 82088102, No. 82171613, No. 82001645), Collaborative Innovation Program of Shanghai Municipal Health Commission (No. 2020CXJQ01), CAMS Innovation Fund for Medical Sciences (No. 2019-I2M-5-064), Clinical Research Plan of SHDC (No. SHDC2020CR1008A), Shanghai Clinical Research Center for Gynecological Diseases (22MC1940200), Shanghai Urogenital System Diseases Research Center (2022ZZ01012), Shanghai Frontiers Science Research Center of Reproduction and Development, and Key Discipline Construction Project (2023–2025) of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (GWVI-11.1-35).