Table1_Association of age at first sexual intercourse and lifetime number of sexual partners with cardiovascular diseases: a bi-directional Mendelian randomization study.docx

BackgroundLimited studies have explored the association between sexual factors [age at first sexual intercourse (AFS) and lifetime number of sexual partners (LNSP)] and cardiovascular diseases (CVDs), leaving the causality inconclusive.
MethodsWe performed a bi-directional Mendelian randomization (MR) study to investigate the causality between sexual factors and CVDs, including coronary artery disease, myocardial infarction, atrial fibrillation (AF), heart failure (HF), and ischemic stroke (IS). Single-nucleotide polymorphisms (SNPs) for sexual factors were extracted from the UK Biobank. Statistics for each CVD were derived from two different databases. MR estimates were calculated per outcome database and were combined through meta-analysis. Several complementary sensitivity analyses were also performed.
ResultsThe primary analysis suggested that AFS was causally associated with the risk of CVDs; the odds ratios (ORs) ranged from 0.686 [95% confidence interval (CI), 0.611–0.770] for HF to 0.798 (95% CI, 0.719–0.886) for AF. However, the association between AFS and IS (OR, 0.844; 95% CI, 0.632–1.126) was not consistent in the meta-analysis after excluding SNPs related to confounders. Moreover, non-significant associations were found between LNSP and CVDs. Reverse direction MR analysis showed that CVDs were not associated with sexual factors.
ConclusionsGenetic evidence suggested that AFS was causally associated with the risk of CVDs except for IS, whereas non-significant association of LNSP with CVDs was detected. Further investigation into AFS could be warranted in preventing the progression of CVDs.

背景
目前针对性相关因素[首次性行为年龄（age at first sexual intercourse, AFS）与终身性伴侣数（lifetime number of sexual partners, LNSP）]与心血管疾病（cardiovascular diseases, CVDs）之间关联的研究较为有限，二者的因果关系尚未明确。
方法
本研究采用双向孟德尔随机化（Mendelian randomization, MR）设计，探究性相关因素与心血管疾病的因果关联，所纳入的心血管疾病包括冠状动脉疾病、心肌梗死、心房颤动（atrial fibrillation, AF）、心力衰竭（heart failure, HF）及缺血性脑卒中（ischemic stroke, IS）。性相关因素的单核苷酸多态性（single-nucleotide polymorphisms, SNPs）数据提取自英国生物银行（UK Biobank）。各类心血管疾病的统计数据来源于两个独立数据库。针对每个结局数据库分别计算MR效应量，并通过荟萃分析合并结果。此外还开展了多项补充敏感性分析。
结果
主分析结果显示，首次性行为年龄与心血管疾病风险存在因果关联；其比值比（odds ratios, OR）范围从心力衰竭的0.686[95%置信区间（95% confidence interval, CI）：0.611~0.770]至心房颤动的0.798（95% CI：0.719~0.886）。但在排除与混杂因素相关的单核苷酸多态性后，荟萃分析中首次性行为年龄与缺血性脑卒中的关联（OR=0.844；95% CI：0.632~1.126）并不稳定。此外，未发现终身性伴侣数与心血管疾病存在显著关联。反向MR分析结果显示，心血管疾病与性相关因素无显著关联。
结论
遗传学证据表明，首次性行为年龄与除缺血性脑卒中外的心血管疾病风险存在因果关联，而未发现终身性伴侣数与心血管疾病存在显著关联。未来可针对首次性行为年龄开展进一步研究，以助力心血管疾病的预防与病程控制。