DataSheet_2_Causal association between obesity and hypothyroidism: a two-sample bidirectional Mendelian randomization study.csv

IntroductionPrevious observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from alternative methodologies to establish a causal link.MethodsWe investigated the causal relationship between obesity and hypothyroidism using a two-sample bidirectional Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) associated with obesity-related traits were extracted from a published genome-wide association study (GWAS) of European individuals. Summarized diagnostic data of hypothyroidism were obtained from the UK Biobank. Primary analyses were conducted using the inverse variance-weighted (IVW) method with a random-effects model as well as three complementary approaches. Sensitivity analyses were performed to ascertain the correlation between obesity and hypothyroidism.ResultsMR analyses of the IVW method and the analyses of hypothyroidism/myxedema indicated that body mass index (BMI) and waist circumference (WC) were significantly associated with higher odds and risk of hypothyroidism. Reverse MR analysis demonstrated that a genetic predisposition to hypothyroidism was associated with an increased risk of elevated BMI and WC, which was not observed between WC adjusted for BMI (WCadjBMI) and hypothyroidism.DiscussionOur current study indicates that obesity is a risk factor for hypothyroidism, suggesting that individuals with higher BMI/WC have an increased risk of developing hypothyroidism and indicating the importance of weight loss in reducing the risk of hypothyroidism.

引言：既往的观察性研究报道了肥胖与甲状腺功能减退症易感性之间的正相关关系；然而，关于建立因果联系的替代方法证据有限。方法：本研究采用双向孟德尔随机化（MR）分析，探讨了肥胖与甲状腺功能减退症之间的因果关系。从欧洲人群的已发表的全基因组关联研究（GWAS）中提取了与肥胖相关性状关联的单核苷酸多态性（SNPs）。从英国生物样本库中获得了甲状腺功能减退症的总结诊断数据。主要分析采用逆方差加权（IVW）方法以及随机效应模型，并辅以三种互补方法。进行了敏感性分析，以确定肥胖与甲状腺功能减退症之间的相关性。结果：IVW方法的MR分析和甲状腺功能减退症/粘液水肿的分析表明，体重指数（BMI）和腰围（WC）与甲状腺功能减退症更高的几率和风险显著相关。反向MR分析显示，甲状腺功能减退症的遗传易感性增加与BMI和WC升高的风险增加相关，而调整BMI的腰围（WCadjBMI）与甲状腺功能减退症之间未见此关联。讨论：本研究结果表明，肥胖是甲状腺功能减退症的风险因素，表明BMI/WC较高的人群患甲状腺功能减退症的风险增加，并指出减重在降低甲状腺功能减退症风险中的重要性。