甲状腺功能和骨质疏松症的关联:欧洲人群全基因组数据分析  

Association between thyroid function and osteoporosis:genome-wide data analysis of European populations

作　　者：曾浩 孙鹏程 柴源 黄有荣[2] 张驰 章晓云[2] Zeng Hao;Sun Pengcheng;Chai Yuan;Huang Yourong;Zhang Chi;Zhang Xiaoyun(Guangxi University of Chinese Medicine,Nanning 530001,Guangxi Zhuang Autonomous Region,China;Department of Orthopedics,Ruikang Hospital,Guangxi University of Chinese Medicine,Nanning 530011,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西中医药大学,广西壮族自治区南宁市530001 [2]广西中医药大学附属瑞康医院骨科,广西壮族自治区南宁市530011

出　　处：《中国组织工程研究》2026年第4期1019-1027,共9页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(82405434),项目负责人:张驰;广西自然科学基金面上项目(2023GXNSFAA026075),项目负责人:章晓云;广西中医药大学博士启动基金(2023BS043),项目负责人:张驰;广西中医药大学青年创新研究团队项目(2021TD001),项目负责人:章晓云;广西中医药适宜技术开发与推广项目(GZSY22-36),项目负责人:章晓云;黄有荣桂派中医大师培养项目(项目文号:桂中医药科教发[2022]6号),项目负责人:黄有荣。

摘　　要：背景:多项观察性研究发现甲状腺功能及其相关疾病与骨质疏松症之间存在密切关系,但其因果关系尚不明确。目的:通过大型汇总遗传数据,采用孟德尔随机化分析来探究遗传预测的甲状腺功能及其相关疾病与骨质疏松症的因果关系。方法:使用全基因组关联研究汇总数据,以逆方差加权法为主要的孟德尔随机化分析方法,同时采用MR-Egger法、加权中位数法、简单模式法和加权模式法,分析甲状腺功能及其相关疾病与骨质疏松症之间的因果关系;并采用两步法中介孟德尔随机化分析,计算药物介导的甲状腺功能障碍对骨质疏松的中介效应及中介比例,最后进行敏感性分析,使用MR-Egger截距测试和MR-PRESSO检测多效性,Cochran’s Q检验检测异质性,留一法进行敏感性分析。结果与结论:(1)逆方差加权法结果显示甲状腺功能对骨密度可产生影响,促甲状腺素、游离三碘甲状腺原氨酸对骨密度、游离甲状腺素、亚临床甲状腺功能亢进症均与骨密度存在因果效应;(2)此外,中介分析显示卡比马唑在甲状腺功能亢进症与骨质疏松症发病风险之间的因果关系中存在潜在中介效应;左旋甲状腺素钠在甲状腺功能减退症与骨质疏松症发病风险之间的因果关系中存在潜在中介效应;(3)综上,正常范围内偏高的促甲状腺素能够增加骨密度,而正常范围内偏高的游离三碘甲状腺原氨酸和游离甲状腺素以及亚临床甲状腺功能亢进症会降低骨密度,并且在甲状腺功能障碍药物治疗时,其骨质疏松症发病风险一定程度上是通过服用治疗药物这一中介路径介导的;(4)此次研究主要聚焦于欧洲人群数据,但鉴于遗传背景的共通性及全基因组数据分析方法的普适性,其对探索中国人群骨质疏松症的发病机制、制定有效干预措施及遗传咨询等方面具有重要的参考和借鉴意义。BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran’s Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are al

关 键 词：甲状腺功能 甲状腺功能障碍 骨质疏松症 骨代谢 骨密度 遗传学 孟德尔随机化 中介分析 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R681.1