男性睾酮与骨质疏松因果关系的两样本孟德尔随机化研究  

Causal effect of testosterone on osteoporosis in men: a two-sample Mendelian randomization

作　　者：黎远帆 颜赟坤[1,2,3] 罗茜倩 温政 陈泽凤 白玉兰 龙新阳 林睿 莫曾南[1,2,3] 徐剑锋 Yuanfan Li;Yunkun Yan;Qianqian Luo;Zheng Wen;Zefeng Chen;Yulan Bai;Xinyang Long;Rui Lin;Zengnan Mo;Jianfeng Xu(Center for Genomic and Personalized Medicine,Guangxi Medical University,Nanning 530021,Guangxi,China;Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine,Nanning 530021,Guangxi,China;Guangxi key Laboratory for Genomic and Personalized Medicine,Nanning 530021,Guangxi,China)

机构地区：[1]广西医科大学基因组与个体化医学研究中心,南宁530021 [2]广西基因组与个体化医学研究协同创新中心,南宁530021 [3]广西基因组与个体化医学研究重点实验室,南宁530021

出　　处：《广西医科大学学报》2020年第4期710-721,共12页Journal of Guangxi Medical University

基　　金：supported by the National Natural Science Foundation of China(81770759);National Key Research and Development Program of China(2017YFC0908000).

摘　　要：目的:运用两样本孟德尔随机化(MR)方法探讨男性血清睾酮水平与骨质疏松的因果关系,以发现新的治疗靶点。方法:以度他雄胺降低睾酮治疗前列腺癌的随机对照试验(n=3 225)的全基因组关联研究数据作为暴露数据集,来自骨质疏松症联盟的股骨颈(FN)和腰椎(LS)骨密度(BMD)的汇总数据(n=3 2965)作为结果数据集。采用逆方差加权法(IVW),MR-Egger回归和加权中位数法评估因果效应关系,其他方法用于敏感性分析。结果:共有3组工具变量:创新组1,创新组2和保守组。保守组IVW结果显示,遗传决定的较高睾酮水平与FN BMD(Beta=-0.07;95%CI:-0.17~0.04)或LS BMD(Beta=-0.06;95%CI:-0.18~0.07)之间没有因果关系。MR-Egger回归证明遗传水平多效性未对因果估计结果造成偏倚,且Q统计量也未显示存在异质性。3个工具变量组在3种MR分析方法中都获得一致结果。结论:血清睾酮水平与骨质疏松在男性人群中未发现有因果关系,这表明改变血清睾酮水平可能不会降低男性骨质疏松的发病风险。Objective: To examine the association between serum testosterone and osteoporosis in male by using Mendelian randomization(MR),so as to find potential targets for treatment.Methods: A two-sample MR analysis which involved three MR methods of inverse variance weighting,MR-Egger regression,and weighted median,was performed to assess the impact of testosterone on the risk of osteoporosis.Reduction by Dutasteride of Prostate Cancer Events randomized controlled trial(n=3225)on testosterone was taken as the exposure dataset,and the Genetic Factors of Osteoporosis Consortium(n=32965)on the femoral neck(FN)and lumbar spine(LS)bone mineral density(BMD)was taken as the outcome dataset.Results: There were three sets of instrument variants: Innovative set 1,Innovative set 2,and Conservative set.When using the Conservative set,the inverse variance weighting method suggested that no causal association between genetically determined higher testosterone status and FN BMD(Beta=-0.07;95% CI:-0.17–0.04)or LS BMD(Beta=-0.06;95% CI:-0.18–0.07).MR-Egger regression demonstrated the null-pleiotropy results,and the Q statistic did not indicate heterogeneity.Consistent results were obtained by using three MR methods and the other two sets.Conclusion: This study shows that serum testosterone has no influence on osteoporosis in male,suggesting that changes in serum testosterone status may not decrease risk of osteoporosis in men.

关 键 词：睾酮 骨质疏松 骨密度 孟德尔随机化 

分 类 号：R589.9[医药卫生—内分泌]