目的:基于"肾其华在发"理论，利用双向孟德尔随机化(Mendelian randomization，MR)分析的方法挖掘自然发色与男性不育风险之间的因果关系。方法:研究数据来自全基因组关联研究(genome-wide association study，GWAS)汇总数据集，包括5种不同自然发色及男性不育患者的GWAS数据。使用逆方差加权法、加权中位数法和MR-Egger回归分析进行双向MR分析，以OR值评估自然发色与男性不育之间的因果关系。使用Cochran Q方法检验异质性，MR-Egger及MR-PRESSO法检验多效性。结果:逆方差加权法的结果表明，自然发色为金色与男性不育风险增高具有因果关系(P=0。003，OR:3。235，95％CI:1。483～7。055)。自然发色为红色和淡棕色与男性不育风险之间无因果关系。自然发色为深棕色(P=0。014，OR:0。559，95％CI:0。352～0。889)及自然发色为黑色(P=0。024，OR:0。099，95％CI:0。013～0。736)与男性不育风险降低具有因果关系。男性不育风险对自然发色无因果效应(P＞0。05)。Cochran Q方法表明本研究所纳入的SNPs不存在异质性(P＞0。05)。MR-Egger及MR-PRESSO方法的结果表明，暴露因素和结局变量之间不存在水平多效性(P＞0。05)。结论:自然发色越浅者患有男性不育的风险越高，自然发色越深者患有男性不育的风险越低。
Causal Relationship Between Natural Hair Color and Male Infertility Based on"Hair Showing Kidney Brilliance"Theory:A Bidirectional Mendelian Randomization Analysis
Objective:Based on the theory of"hair showing Kidney brilliance",the causal relationship between natural hair color and male infertility risk was investigated by two-way Mendelian randomization(MR)analysis.Methods:The study data were obtained from the genome-wide association study(GWAS)pooled dataset,including five different natural hair colors and GWAS data of male infer-tility patients.Two-way MR analyses were performed using the inverse variance weighting method,weighted median method,and MR-Egger regression analysis to assess the causal relationship between natural hair color and male infertility in terms of ORs.Heterogeneity was tested using the Cochran Q method,and multivariate validity was tested by MR-Egger and MR-PRESSO methods.Results:The results of the inverse variance weighting method showed that natural hair color blonde was causally associated with increased risk of male infertility(P=0.003,OR:3.235,95％CI:1.483-7.055).There was no causal association between natural hair color of red and light brown and risk of male infertility.Natural hair color of dark brown(P=0.014,OR:0.559,95％CI:0.352-0.889)and natural hair color of black(P=0.024,OR:0.099,95％CI:0.013-0.736)were causally associated with reduced risk of male infertility.There was no causal effect of male infertility risk on natural hair color(P＞0.05).The Cochran Q method showed that there was no heterogeneity in the SNPs included in this study(P＞0.05).The results of the MR-Egger(P＞0.05)and MR-PRESSO methods(P＞0.05)showed that there was no horizontal pleiotropy between the exposure factors and outcome variables.Conclusion:The risk of male infertility is higher in those with lighter natural hair color and lower in those with darker natural hair color.
male infertilitynatural hair colorMendelian randomizationhair showing Kidney brilliance
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