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两样本孟德尔随机化研究肥胖与男性不育症的因果关系

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目的:通过孟德尔随机化(MR)研究阐明肥胖与男性不育症(MI)之间的因果关系.方法:进行双样本MR分析,以评估遗传预测的体质量指数(BMI)与MI风险的因果关联.暴露因子为BMI(n病例组=99 998,n对照组=12 746).MI的遗传信息来自一项全基因组关联研究(GWAS),该研究包含73 479例欧洲人.在单变量孟德尔随机化研究(UVMR)分析中,将逆方差加权法(IVW)作为主要方法,MR-Egger回归模型和加权中值估计模型作为因果推断的补充方法.其次,运用多种敏感性分析方法来验证 MR 结果的稳健性,包括Cochran's Q检验、MR-Egger 截距检验、MR-PRESSO、留一法检验和漏斗图.为了评估BMI对MI风险的直接因果效应,进行多变量孟德尔随机化研究(MVMR).结果:UVMR 发现遗传预测BMI与MI风险增加之间存在因果关系(OR:1.237,95%CI:1.090~1.404,P=0.001).敏感性分析发现,目前的研究几乎不存在偏倚(P>0.05).在调整 2 型糖尿病、饮酒和吸烟等危险因素后,MVMR进一步证实遗传预测的BMI对MI风险增加有直接影响(P均<0.05).结论:两样本MR研究表明,遗传预测的BMI可能与MI风险增加之间存在因果关系.未来的研究可基于这一发现,进一步探讨肥胖与MI两者之间因果关系的具体机制,为预防和治疗提供新途径.
Causal relationship between obesity and male infertility:A two-sample Mendelian randomization study
Objective:To clarify the causal relationship between obesity and male infertility through Mendelian randomization(MR)study.Methods:We assessed the causal effect of genetically predicted body mass index(BMI)on the risk of male infertility via a two-sample MR analysis,with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans.In the univariable MR(UVMR)analysis of the causal relationship,we mainly used inverse variance weighting(IVW),with MR-Egger regression and weighted median filtering as the supplementary methods.Sensitivity analyses including the Cochran's Q test,Egger intercept test,MR-PRESSO,leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results.To evaluate the direct causal effects of BMI on MI risk,mult-ivariable MR(MVMR)was performed.Results:UVMR indicated a causal relationship between genetically predicted BMI and an in-creased risk of male infertility(OR:1.237,95%CI:1.090-1.404,P=0.001).Sensitivity analysis revealed little evidence of bias in the current study(P>0.05).With such risk factors as type 2 diabetes,alcohol consumption and smoking adjusted,MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility(P<0.05).Conclusion:Genetically pre-dicted BMI may be associated with an increased risk of male infertility.Further studies are expected to explore the underlying mecha-nisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.

obesitybody mass indexcausalitymale infertilityMendelian randomization

李智超、滕志海、韩振伟、张艳平、金成根、王亚轩

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河北医科大学第二医院泌尿外科,河北 石家庄 050000

肥胖 体质量指数 因果关系 男性不育症 孟德尔随机化研究

2024

中华男科学杂志
南京军区南京总医院

中华男科学杂志

CSTPCD
影响因子:1.052
ISSN:1009-3591
年,卷(期):2024.30(4)