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孟德尔随机化研究甲状腺功能减退症与骨质疏松症的因果关系

A Mendelian randomization study on the causal relationship between hypothyroidism and osteoporosis
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摘要 目的为研究甲状腺功能减退症(hypothyroidism)与骨质疏松症(osteoporosis,OP)之间潜在的关联,采用单变量及多变量孟德尔随机化(Mendelian randomization,MR)方法进行因果推断。方法从公开数据库下载甲状腺功能减退症和OP的全基因组关联研究(genome-wide association study,GWAS)数据,主要采用逆方差加权(inverse-variance weighted,IVW)法评估甲状腺功能减退症相关表型与OP发生风险的因果关联,并补充应用加权中值法、MR-Egger法和最大似然比法来评估结果的稳健性,另外采用MR-PRESSO法,Cochran’s Q检验等进行敏感性分析。结果IVW法结果显示遗传预测的甲状腺功能减退症与OP的发生风险之间存在因果关联(OR=8.701,95%CI:1.546~48.961,P=0.014),最大似然比法显示出了一致的结果,多变量MR分析显示,甲状腺功能减退症与OP的因果关联在考虑三酰甘油、体质指数(body mass index,BMI)、糖尿病、吸烟和饮酒后仍然存在。结论遗传学预测的甲状腺功能减退症与OP发生风险升高有关。 Objective To investigate the potential association between hypothyroidism and osteoporosis(OP),univariate and multivariate Mendelian randomization(MR)method were used for causal inference.Methods Retrieve genome-wide association study(GWAS)data on hypothyroidism and osteoporosis(OP)from publicly available databases.Utilise the inverse variance weighted(IVW)method as the primary approach to assess the causal association between hypothyroidism-related traits and the risk of OP.Additionally,employ the weighted median method,MR Egger method,and maximum likelihood ratio method to assess the reliability and consistency of the findings.In addition,the MR-PRESSO method was employed,and sensitivity analysis was performed using Cochran’s Q test and other techniques.Results The IVW approach result indicated a causal association between genetic prediction of hypothyroidism and the risk of OP(OR=8.701,95%CI:1.546~48.961,P=0.014).The method of highest likelihood ratio consistently yielded reliable outcomes.Through multivariable MR analysis,it was determined that the causative association between hypothyroidism and OP remained significant even after accounting for lipids,body mass index(BMI),diabetes,smoking,and alcohol consumption.Conclusion Genetically determined hypothyroidism is linked to a higher likelihood of developing osteoporosis.
作者 吴天强 韩昕宇 王业 刘春燕 赵娜 马建 WU Tianqiang;HAN Xinyu;WANG Ye;LIU Chunyan;ZHAO Na;MA Jian(Heilongjiang University of Chinese Medicine,Harbin 150000,China;The First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,China)
出处 《中国骨质疏松杂志》 北大核心 2025年第6期855-861,共7页 Chinese Journal of Osteoporosis
基金 黑龙江省中医药管理局省级名中医专家传承工作室建设项目(2018) 黑龙江省中医药管理局资助项目(ZYW2022-003)。
关键词 孟德尔随机化 甲状腺功能减退症 骨质疏松症 因果关系 Mendelian randomization hypothyroidism osteoporosis causality
作者简介 通信作者:马建,Email:majian1961@163.com。
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