目的 探究多囊卵巢综合征(polycystic ovary syndrome,PCOS)与骨密度(bone mineral density,BMD)之间的因果关系,从而为PCOS患者及时采取措施防治骨质疏松提供依据.方法 基于公开发表的欧洲人群PCOS与全身BMD全基因组关联研究(genome-wide association study,GW AS)汇总数据,运用两样本孟德尔随机化(MR)探究PCOS与BMD之间的因果关联.采用与PCOS相关的遗传位点作为工具变量,使用逆方差加权法(IVW)作为主要分析方法进行MR分析,以比值比(OR)评价PCOS与全身BMD之间的因果关系;采用异质性检验、多效性检验和留一法进行敏感性分析,以评估分析结果的稳健性.结果 共纳入68个单核苷酸多态性(SNP)作为工具变量,IVW法结果显示PCOS与全身BMD降低的风险相关(OR=1.010,95％CI:1.000～1.019,P=0.041).敏感性分析结果稳健,SNP不存在水平多效性和异质性.结论 PCOS与全身BMD的降低存在因果关系,提示PCOS患者应密切关注BMD,及时采取预防骨质疏松的措施.
Causal relationship between polycystic ovary syndrome and bone mineral density:a Mendelian randomization study
Objective To investigate the causal relationship between polycystic ovary syndrome(PCOS)and bone min-eral density(BMD),so as to provide a basis for PCOS patients to take timely measures to prevent and treat osteoporo-sis.Methods Based on the published genome-wide association studies(GWAS)of PCOS and systemic BMD in the European population,two samples of Mendelian randomization were used to explore the causal relationship between P-COS and BMD.Genetic loci associated with PCOS were used as instrumental variables,and inverse variance weighting(IVW)was used as the main analysis method to conduct Mendelian randomization(MR)analysis,and odds ratio(OR)was used to evaluate the causal relationship between PCOS and BMD.Heterogeneity test,pleiotropy test and leave-one-out method were used for sensitivity analysis to evaluate the robustness of the analysis results.Results A total of 68 single nucleotide polymorphisms(SNPs)were included as instrumental variables,and the IVW method showed that PCOS was associated with a risk of reduced systemic BMD(OR=1.010,95％Cl:1.000-1.019,P=0.041).The sensitivity analysis results are robust,and there was no horizontal pleiotropy or heterogeneity in SNPs.Conclusion There is a causal relationship between PCOS and systemic BMD reduction,suggesting that PCOS patients should pay close attention to BMD and take timely measures to prevent osteoporosis.
Polycystic ovary syndromeBone mineral densityMendelian randomisationCausalityGenome-wide association study
NETL
NSTL
万方数据
