东亚人群甲状腺疾病与骨质疏松症因果关系的孟德尔随机化研究  

Mendelian randomization study on the causal relationship between thyroid disease and osteoporosis in an East Asian population

作　　者：刘浩[1] 阎伟[2] 骆帝 李金松[2] 闫德志 丁丑 胡铖波 LIU Hao;YAN Wei;LUO Di;LI Jinsong;YAN Dezhi;DING Chou;HU Chengbo(Shandong University of Traditional Chinese Medicine,Jinan 250013,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250013,China)

机构地区：[1]山东中医药大学,山东济南250013 [2]山东中医药大学附属医院,山东济南250013

出　　处：《中国骨质疏松杂志》2025年第2期182-187,共6页Chinese Journal of Osteoporosis

基　　金：山东省自然科学基金联合专项项目(ZR2021LZY002);山东省医药卫生科技发展计划(202104070600);2020年齐鲁卫生与健康杰青人才培育工程(rc2021002-23)。

摘　　要：目的采用两样本孟德尔随机化方法分析东亚人群甲状腺功能亢进症、甲状腺功能减退症、Graves病、桥本甲状腺炎与骨质疏松症发病风险的因果关联。方法甲亢、甲减、Graves病、桥本甲状腺炎为暴露因素,骨质疏松症为结局因素,研究人群限定为东亚人群,分别获得12、10、19、7个单核苷酸多态性(single nucleotide polymorphisms,SNPs)作为工具变量纳入研究。逆方差加权(inverse variance weighted,IVW)、MR-Egger回归和加权中位数法(weighted median,WM)用于分析四种甲状腺疾病与骨质疏松症风险之间的因果关系。Cochran Q检验和漏斗图用于检测异质性,MR-Egger回归和MR-PRESSO用于检验水平多效性和离群值。结果IVW分析发现遗传预测的甲亢(OR=1.054,95%CI:1.013~1.097,P=0.010)、Graves病(OR=1.052,95%CI:1.019~1.086,P=0.002)与骨质疏松症发病风险显著增加有关;桥本甲状腺炎与骨质疏松症之间存在潜在因果效应(OR=1.047,95%CI:1.002~1.095,P=0.040);甲减与骨质疏松症发病风险没有因果关系(OR=1.002,95%CI:0.943~1.065,P=0.942)。其他分析方法支持此结论。敏感性分析表明结果具有稳健性。结论在东亚人群中,遗传预测的甲亢、Graves病与罹患骨质疏松症的风险增加有因果关系,而甲减的高遗传风险不会增加骨质疏松症的发病风险。Objective To analyze the causal relationship between hyperthyroidism,hypothyroidism,Graves’disease,Hashimoto thyroiditis and the risk of developing osteoporosis in an East Asian population using a two-sample Mendelian randomization method.Methods Hyperthyroidism,hypothyroidism,Graves’disease and Hashimoto thyroiditis were the exposure factors,osteoporosis was the outcome factor,and the study population was limited to the East Asian population.12,10,9,and 7 single nucleotide polymorphisms(SNPs)were obtained for inclusion in the study as instrumental variables,respectively.Inverse variance weighted(IVW),MR-Egger regression,and weighted median(WM)method were used to analyze the causal relationship between 4 thyroid disorders and osteoporosis risk.Cochran Q-tests and funnel plots were used to detect heterogeneity,and MR-Egger regression and MR-PRESSO were used to test for horizontal pleiotropy and outliers.Results IVW analysis identified genetically predicted hyperthyroidism(OR=1.054,95%CI:1.013-1.097,P=0.010)and Graves’disease(OR=1.052,95%CI:1.019-1.086,P=0.002)were associated with a significantly increased risk of developing osteoporosis.There was a potential causal effect between Hashimoto’s thyroiditis and osteoporosis(OR=1.047,95%CI:1.002-1.095,P=0.040).Hypothyroidism was not causally associated with the risk of developing osteoporosis(OR=1.002,95%CI:0.943-1.065,P=0.942).Other method of analysis supported this conclusion.Sensitivity analyses indicated the robustness of the result.Conclusion In East Asian populations,genetically predicted hyperthyroidism and Graves’disease were causally associated with an increased risk of developing osteoporosis,whereas a high genetic risk of hypothyroidism did not increase the risk of developing osteoporosis.

关 键 词：孟德尔随机化 甲状腺疾病 骨质疏松症 遗传变异 因果关联 

分 类 号：R581[医药卫生—内分泌] R589[医药卫生—内科学]