摘要
目的采用孟德尔随机化(Mendelian randomization,MR)方法研究甲状腺功能减退症(Hypothyroidism)与多囊卵巢综合征(Polycystic ovarian syndrome,PCOS)之间的双向因果关系。方法根据预设的阈值从甲状腺功能减退症的全基因组关联研究数据(Genome-wide association study,GWAS)中提取出与其强相关的独立单核苷酸多态性位点(Single nucleotide polymorphism,SNP)作为工具变量,主要采用逆方差加权法(inverse-variance weighted,IVW)评估甲状腺功能减退症相关表型与PCOS发生风险的关联;同时采用Cochran Q检验评估SNP的异质性。使用MR-PRESSO检验检测是否存在离群的SNP。MR-Egger截距测试检验SNP的水平多效性。“留一法”敏感性分析检验MR结果是否受单个SNP的影响。结果共筛选到141个与甲状腺功能减退症相关的SNP,IVW分析法显示甲状腺功能减退症和PCOS之间存在因果关系(OR=16.725,95%CI:1.153~242.547,P=0.038),Cochran Q检验结果显示Q=154.690,P=0.187,表明纳入分析的SNP之间不存在异质性,MR-Egger截距为0.0068(P=0.614),表明筛选得到的SNP不存在基因多效性,MR-PRESSO未发现离群的SNP,“留一法”敏感性分析显示,因果估计不太可能受到某些SNP效应的影响,反向MR分析的结果不支持反向因果关系。结论遗传学预测的甲状腺功能减退症与PCOS发生风险升高有关。
Objective To investigate the bidirectional causality between hypothyroidism and polycystic ovarian syndrome(PCOS)using a Mendelian randomization(MR)approach.Methods Independent single nucleotide polymorphisms(SNP)loci strongly associated with hypothyroidism were extracted from genome-wide association study(GWAS)data according to predefined thresholds as instrumental variables,the association between hypothyroidism-related phenotypes and the risk of PCOS was assessed mainly by the inverse variance weighting(IVW)method;the heterogeneity of SNPs was also assessed by the Cochran Q test.The presence of outlier SNPs was detected using the MR-PRESSO test;the MR-Egger intercept test examined the horizontal pleiotropy of SNPs.The sensitivity analysis of the"leave-one-out"method was used to test whether the MR results were influenced by individual SNPs.Results A total of 141 SNPs associated with hypothyroidism were screened,and IVW analysis showed a causal relationship between hypothyroidism and PCOS(OR=16.725,95%CI:1.153-242.547,P=0.038).The Cochran Q-test results showed Q=154.690,P=0.187,indicating no heterogeneity between the SNPs included in the analysis,the MR-Egger intercept was 0.0068(P=0.614),indicating that the screened SNPs were not genetically pleiotropic,and no outlier SNP was found by MR-PRESSO.Causal estimates were unlikely to be influenced by certain SNP effects according to the sensitivity analysis of the"leave-one-out"method,and the results of the reverse MR analysis did not support reverse causality.Conclusion Genetically predicted hypothyroidism is associated with an elevated risk of developing PCOS.
作者
韩昕宇
吴天强
冯晓玲
HAN Xin-yu;WU Tian-qiang;FENG Xiao-ling(Heilongjiang University of Traditional Chinese Medicine,Harbin,Heilongjiang 150040,China;不详)
出处
《现代预防医学》
CAS
北大核心
2023年第16期2881-2884,2897,共5页
Modern Preventive Medicine
基金
国家自然科学基金面上项目(81973894,82174421)。
作者简介
韩昕宇(1996-),女,博士在读,研究方向:多囊卵巢综合征等生殖内分泌疾病的防治;通信作者:冯晓玲,E-mail:doctorfxl@163.com。
