Hu Mengjin, Wang Xiaoning, Tan Jiangshan, Yang Jingang, Gao Xiaojin, Yang Yuejin
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China.
School of Medicine, Shandong University, Jinan 250012, China.
J Cardiovasc Dev Dis. 2022 Jul 26;9(8):233. doi: 10.3390/jcdd9080233.
Observational studies have suggested that paternal longevity is associated with reduced risks of cardiovascular diseases, yet the causal association remains to be determined.
To investigate whether Mendelian randomization (MR) results support a causal role of paternal longevity for risks of cardiovascular diseases.
Genetic variants associated with paternal longevity and cardiovascular diseases were obtained from public genome-wide association study data. We used inverse variance weighted MR under a random-effects model to provide causal estimates between paternal longevity and cardiovascular diseases.
Paternal longevity was associated with decreased risks of coronary heart disease (odds ratio (OR): 0.08; 95% confidence interval (CI): 0.02-0.37; = 0.001) and peripheral artery disease (OR: 0.15; 95% CI: 0.03-0.65; = 0.011). No significant differences were observed in hypertension, atrial fibrillation, heart failure, transient ischemic attack, ischemic stroke, or cardiac death. The weighted median method revealed consistent results between genetically instrumented paternal longevity and decreased risk of coronary heart disease and peripheral artery disease. No significant differences were observed in the MR-Egger results. Multivariable MR consistently indicated causal associations between paternal longevity and decreased cardiovascular diseases. The leave-one-out analysis suggested that the causal associations were not affected by individual single-nucleotide polymorphisms. The intercept of the MR-Egger estimator and funnel plot revealed no indication of horizontal pleiotropic effects.
Our MR analyses supported a causal role of paternal longevity for decreased risks of coronary heart disease and peripheral artery disease, which highlighted the need for better monitoring and intervention of cardiovascular diseases in populations with premature paternal death.
观察性研究表明，父亲长寿与心血管疾病风险降低有关，但因果关系仍有待确定。
研究孟德尔随机化（MR）结果是否支持父亲长寿对心血管疾病风险的因果作用。
从公开的全基因组关联研究数据中获取与父亲长寿和心血管疾病相关的基因变异。我们在随机效应模型下使用逆方差加权MR来提供父亲长寿与心血管疾病之间的因果估计。
父亲长寿与冠心病风险降低相关（比值比（OR）：0.08；95%置信区间（CI）：0.02 - 0.37；P = 0.001）和外周动脉疾病风险降低相关（OR：0.15；95%CI：0.03 - 0.65；P = 0.011）。在高血压、心房颤动、心力衰竭、短暂性脑缺血发作、缺血性中风或心源性死亡方面未观察到显著差异。加权中位数法显示，基因检测的父亲长寿与冠心病和外周动脉疾病风险降低之间结果一致。MR-Egger结果未观察到显著差异。多变量MR始终表明父亲长寿与心血管疾病风险降低之间存在因果关联。留一法分析表明，因果关联不受单个单核苷酸多态性的影响。MR-Egger估计器的截距和漏斗图未显示水平多效性效应的迹象。
我们的MR分析支持父亲长寿对降低冠心病和外周动脉疾病风险具有因果作用，这突出了对父亲过早死亡人群中心血管疾病进行更好监测和干预 的必要性。
