Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Front Endocrinol (Lausanne). 2024 Apr 15;15:1338077. doi: 10.3389/fendo.2024.1338077. eCollection 2024.
Stroke is a devastating global health issue, with high mortality and disability rates. The increasing prevalence of male infertility among reproductive-aged men has become a growing concern worldwide. However, the relationship between male infertility and stroke incidence remains uncertain. This study aimed to address this knowledge gap by employing a Mendelian randomization (MR) approach.
Utilizing genetic instrumental variables derived from a genome-wide association study (GWAS) on male infertility and stroke, a two-sample MR design was implemented. Five different analysis methods, with inverse-variance weighted as the primary approach, were used to examine the genetic causal associations between male infertility and various stroke subtypes. Heterogeneity analysis, pleiotropy tests, and leave-one-out validation were conducted to assess heterogeneity, evaluate pleiotropy, and ensure the robustness of the findings.
The results indicate a potential lower risk of small vessel stroke associated with male infertility (odds ratio, 95% confidence interval: 0.82, 0.68 to 0.99, =0.044), although no significant impact on other stroke subtypes was observed. The study exhibited low heterogeneity and no apparent pleiotropy; however, the stability of the results was not optimal.
Male infertility might potentially confer a protective effect against small vessel stroke risk. Caution is warranted due to potential confounding factors. Additional studies are necessary to confirm these findings and provide further validation.
中风是一种具有高死亡率和致残率的全球性健康问题。在生殖年龄段的男性中，男性不育症的患病率不断上升，已成为全球日益关注的问题。然而，男性不育症与中风发病率之间的关系尚不确定。本研究旨在通过孟德尔随机化（MR）方法来解决这一知识空白。
利用男性不育症和中风的全基因组关联研究（GWAS）得出的遗传工具变量，采用两样本 MR 设计。使用五种不同的分析方法，以逆方差加权作为主要方法，研究男性不育症与各种中风亚型之间的遗传因果关系。进行异质性分析、多效性检验和单倍型缺失验证，以评估异质性、评估多效性并确保研究结果的稳健性。
结果表明，男性不育症与小血管性中风的风险呈负相关（比值比，95%置信区间：0.82，0.68 至 0.99，=0.044），尽管对其他中风亚型没有显著影响。研究显示出低异质性和无明显的多效性；然而，结果的稳定性并不理想。
男性不育症可能对小血管性中风的风险具有保护作用。由于潜在的混杂因素，需要谨慎对待。需要进一步的研究来证实这些发现并提供进一步的验证。
