基于孟德尔随机化探究阻塞性睡眠呼吸暂停和男性不育症的因果关系

Exploring the causal relationship between obstructive sleep apnea and male infertility using Mendelian randomization

目的 探讨阻塞性睡眠呼吸暂停(OSA)与男性不育症(MI)之间的关联性,应用两样本孟德尔随机化(MR)方法评估OSA对MI的因果影响。方法 对包含25 062例睡眠呼吸暂停病例、172 050例打鼾病例和313 372名对照的全基因组关联研究(GWAS)以及从FinnGen中提取的男性不育症汇总数据(1 271例病例和119 297例对照)进行两样本MR分析。MR分析以逆方差加权法(IVW)作为主要分析方法,以MR-egger回归、加权中位数法(Weighted median)、简单模型(Simple mode)、加权模式(Weighted mode)等方法作为IVW结果的补充证据,同时进行水平多效性和异质性检验以确保结果的稳定性。结果 使用IVW方法没有发现强有力的证据表明OSA对MI发病率有影响(OR=1.617,95%CI:0.823~3.177,P=0.163),且MR-Egger、Weighted median、Simple mode和Weighted mode方法结果与其一致。结论 大型MR分析提示阻塞性睡眠呼吸暂停与男性不育症之间可能不存在因果关系。

Objective To explore the relationship between obstructive sleep apnea(OSA)and male infertility(MI)and evaluate the potential causal effect of OSA on MI through a two⁃sample Mendelian randomization(MR)analysis.Methods Two⁃sample MR analysis was conducted using genome⁃wide association study(GWAS)data,including 25062 cases of SA,172050 cases of snoring,and 313372 controls,as well as summary data extracted from FinnGen for male infertility(1271 cases and 119297 controls).The primary analytical method was the inverse variance⁃weighted(IVW)approach,supplemented by MR⁃Egger regression,weighted median,simple mode,and weighted mode to provide additional evidence corroborating the IVW results.Tests for horizontal pleiotropy and heterogeneity were performed to ensure result stability.Results There was no substantial evidence supporting an association between OSA and MI incidence using the IVW method(OR=1.617,95%CI:0.823⁃3.177,P=0.163).The result of MR⁃Egger,weighted median,simple mode,and weighted mode methods were consistent with the results of the IVW method.Conclusion The large MR analysis indicated that obstructive sleep apnea may not be causally associated with a risk of male infertility.