Childless men are reported to have a higher risk of cardiovascular disease (CVD) and mortality. Information on inherited genetic risk for CVD has improved the predictive models. Presuming that childlessness is a proxy of infertility we aimed to investigate if childless men inherit more often genetic traits for CVD and if combining genetic and parenthood information improves predictive models for CVD morbidity and mortality. Data was sourced from a large prospective population-based cohort where genetic risk score (GRS) was calculated using two sets of either 27 (GRS 27) or 50 (GRS 50) single nucleotide polymorphisms (SNPs) previously found to be associated with CVD. Part of the participants (n = 2572 men) were randomly assigned to a sub-cohort with focus on CVD which served as an exploratory cohort. The obtained statistically significant results were tested in the remaining (confirmatory) part of the cohort (n = 9548 men). GRS distribution did not differ between childless men and fathers (p-values for interaction between 0.29 and 0.76). However, when using fathers with low GRS as reference high GRS was a strong predictor for CVD mortality, the HR (95% CI) increasing from 1.92 (1.10–3.36) for GRS 50 and 1.54 (0.87–2.75) for GRS 27 in fathers to 3.12 (1.39–7.04) for GRS50 and 3.73 (1.75–7.99) for GRS27 in childless men. The confirmatory analysis showed similar trend. Algorithms including paternal information and GRS were more predictive for CVD mortality at 5 and 10 years follow-ups when compared to algorithms including GRS only (AUC 0.88 (95% CI 0.84–0.92) and 0.86 (95% CI 0.84–0.90), and, AUC 0.81 (95% CI 0.75–0.87) and 0.78 (95% CI 0.73–0.82), respectively). Combining information on parental status and GRS for CVD may improve the predictive power of risk algorithms in middle-aged men. Childless men and those with severe infertility problem may be an important target group for prevention of CVD.

据报道，无子女男性患心血管疾病（CVD）和死亡的风险较高。有关 CVD 遗传风险的信息改进了预测模型。假设无子女是不孕不育的一个指标，我们的目的是调查无子女的男性是否更容易遗传心血管疾病的遗传特征，以及结合遗传和父母信息是否可以改善心血管疾病发病率和死亡率的预测模型。数据来源于大型前瞻性人群队列，其中遗传风险评分 (GRS) 使用两组先前发现与 CVD 相关的 27 个 (GRS 27) 或 50 个 (GRS 50) 单核苷酸多态性 (SNP) 进行计算。部分参与者（n = 2572 名男性）被随机分配到一个以 CVD 为重点的子队列，作为探索性队列。所获得的具有统计学意义的结果在队列的其余（确认）部分（n = 9548 名男性）中进行了测试。无子女男性和父亲之间的 GRS 分布没有差异（交互作用的 p 值在 0.29 和 0.76 之间）。然而，当使用低 GRS 的父亲作为参考时，高 GRS 是 CVD 死亡率的强预测因子，父亲的 HR (95% CI) 从 GRS 50 的 1.92 (1.10–3.36) 增加到 GRS 27 的 1.54 (0.87–2.75)。对于无子女男性，GRS50 为 3.12 (1.39–7.04)，GRS27 为 3.73 (1.75–7.99)。验证性分析显示出类似的趋势。与仅包含 GRS 的算法相比，包含父亲信息和 GRS 的算法更能预测 5 年和 10 年随访时的 CVD 死亡率（AUC 0.88 (95% CI 0.84–0.92) 和 0.86 (95% CI 0.84–0.90)，并且，AUC 分别为 0.81 (95% CI 0.75–0.87) 和 0.78 (95% CI 0.73–0.82)。 结合父母状况和 CVD 的 GRS 信息可能会提高中年男性风险算法的预测能力。无子女男性和有严重不育问题的男性可能是预防CVD的重要目标群体。