Supplementary Material for: The causal effect of obesity on the risk of 15 autoimmune diseases: a Mendelian randomization study

Introduction: Observational studies have shown that obesity is a risk factor for various autoimmune diseases. However, the causal relationship between obesity and autoimmune diseases is unclear. Mendelian randomization (MR) was used to investigate the causal effects of obesity on 15 autoimmune diseases. Methods: MR analysis employed instrumental variables, specifically single nucleotide polymorphisms associated with obesity measures such as body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio. The study utilized UK Biobank and FinnGen data to estimate the causal relationship between obesity and autoimmune diseases. Results: Genetically predicted BMI was associated with risk for five autoimmune diseases. The odds ratio per 1-SD increase in genetically predicted BMI, the OR was 1.28 (95% CI, 1.18–1.09; P<0.001) for asthma, 1.37 (95% CI, 1.24–1.51; P<0.001) for hypothyroidism, 1.52 (95% CI, 1.27–1.83; P<0.001) for psoriasis, 1.22 (95% CI, 1.06–1.40; P=0.005) for rheumatoid arthritis, and 1.55 (95% CI, 1.32–1.83; P<0.001) for type 1 diabetes. However, after adjusting for genetic susceptibility to drinking and smoking, the correlation between BMI and rheumatoid arthritis was not statistically significant. Genetically predicted waist circumference, hip circumference, and waist and hip circumference were associated with 6, 6, and 1 autoimmune disease, respectively. Conclusion: This study suggests that obesity may be associated with an increased risk of several autoimmune diseases, such as asthma, hypothyroidism, psoriasis, rheumatoid arthritis, and type 1 diabetes.

引言：观察性研究表明，肥胖是多种自身免疫性疾病的危险因素。然而，肥胖与自身免疫性疾病之间的因果关系尚不明确。本研究采用孟德尔随机化（Mendelian randomization, MR）方法，探究肥胖对15种自身免疫性疾病的因果效应。
方法：孟德尔随机化分析采用工具变量，即与肥胖相关指标（如体质量指数（body mass index, BMI）、腰围、臀围以及腰臀比）相关的单核苷酸多态性（single nucleotide polymorphisms）。本研究利用英国生物库（UK Biobank）和芬兰基因研究队列（FinnGen）数据，评估肥胖与自身免疫性疾病之间的因果关系。
结果：遗传预测的BMI与5种自身免疫性疾病的发病风险相关。遗传预测的BMI每增加1个标准差（SD），哮喘的优势比（odds ratio, OR）为1.28（95%置信区间（confidence interval, CI）：1.18~1.09；P<0.001），甲状腺功能减退症为1.37（95%CI：1.24~1.51；P<0.001），银屑病为1.52（95%CI：1.27~1.83；P<0.001），类风湿关节炎为1.22（95%CI：1.06~1.40；P=0.005），1型糖尿病为1.55（95%CI：1.32~1.83；P<0.001）。然而，在校正饮酒和吸烟的遗传易感性后，BMI与类风湿关节炎之间的相关性无统计学意义。遗传预测的腰围、臀围以及腰臀比分别与6种、6种和1种自身免疫性疾病相关。
结论：本研究表明，肥胖可能与多种自身免疫性疾病的发病风险升高相关，包括哮喘、甲状腺功能减退症、银屑病、类风湿关节炎以及1型糖尿病。