Genetic liability to age at first sex and birth in relation to cardiovascular diseases: a Mendelian randomization study

作者：Miao Chen, Zhen Wang, Hongfei Xu, Xiaofang Chen, Peng Teng, Liang Ma · 发表于：BMC Medical Genomics · 年份：2023 · DOI：10.1186/s12920-023-01496-w · 被引用次数：12 · 研究领域：Birth, Development, and Health、Genetic Associations and Epidemiology、BRCA gene mutations in cancer

Abstract Background Growing evidence suggests that various reproductive factors, including early menarche, early menopause, and age at first birth, may increase the risk of developing cardiovascular disease (CVD) later in life. However, the associations between reproductive factors and CVDs are inconsistent and controversial. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to explore the potential links between age at first sex (AFS) and age at first birth (AFB) and several CVDs. Methods We obtained summary statistics for exposure from the largest genome-wide association studies of AFS and AFB. To serve as instrumental variables, we selected 259 SNPs associated with AFS and 81 SNPs associated with AFB at the genome-wide significance level. We employed a random-effects inverse-variance weighted method to pool estimates, and conducted multivariable MR analysis to determine the direct association between AFS and AFB with CVDs, while accounting for the effects of confounders. Results The genetic liability to later AFS was associated with decreased risks of heart failure (odd ratio [OR] 0.700; 95% confidence interval [CI] 0.639–0.767; p = 2.23 × 10 −14 ), coronary artery disease (OR 0.728; 95% CI 0.657–0.808; p = 1.82 × 10 −9 ), myocardial infarction (OR 0.731; 95% CI 0.657–0.813; p = 8.33 × 10 −9 ), stroke (OR 0.747; 95% CI 0.684–0.816; p = 6.89 × 10 −11 ), and atrial fibrillation (OR 0.871; 95% CI 0.806–0.941; p = 4.48 × 10 −4 ). The genetic liability ...