类风湿关节炎与2型糖尿病风险的两样本孟德尔随机化研究

A two-sample Mendelian randomized study of the rheumatoid arthritis and risk of type 2 diabetes

目的 探讨类风湿关节炎(rheumatoid arthritis,RA)与2型糖尿病(type 2 diabetes,T2D)风险的因果关系。方法 使用公开的RA全基因组关联研究(genome-wide association study,GWAS)汇总数据集为暴露因素,2型糖尿病为结局变量;运用逆方差加权法、加权中位数法、MR-Egger回归法、简单模式和加权模式进行两样本孟德尔随机化(two-sample Mendelian randomization,TSMR)分析。结果 选择了9个单核苷酸多态性作为工具变量,逆方差加权法支持RA与T2D风险之间的因果关系(OR=1.10,95%CI:1.07~1.12);MR-Egger回归法表明也存在因果关联(OR=1.11,95%CI:1.08~1.14)。加权模式:OR=1.10,95%CI:1.08~1.12;简单模式:OR=1.12,95%CI:1.06~1.18;加权众数法:OR=1.10,95%CI:1.08~1.13。工具变量之间可认为不存在异质性与水平多效性;使用“留一法”进行敏感性分析,因果效应稳健。结论 TSMR分析结果支持RA与T2D风险增加存在因果关系。

Objective:To explore the causal relationship between rheumatoid arthritis and the risk of type 2 diabetes(T2D).Methods:The published genome-wide association studies-wide association study(GWAS)pooled data set was used as the exposure factor and T2D as the outcome variable.Two-sample Mendelian randomization (TSMR) analysis was performed using inverse variance weighted,weighted median,MR-Egger regression,simple mode,and weighted mode methods.Results:Nine SNPs were selected as the instrumental variables,and the inverse variance weighted method supported the causal relationship between rheumatoid arthritis and risk of T2D(OR=1.10,95%CI:1.07-1.12).MR-Egger regression also showed a causal association(OR=1.11,95%CI:1.08-1.14).Weighted median:OR=1.10,95%CI:1.08-1.12;Simple mode:OR=1.12,95%CI:1.06-1.18;Weighted mode:OR=1.10,95%CI:1.08-1.13.It could be considered that there was no heterogeneity and horizontal pleiotropic effect between instrumental variables;The causal effect was robust using the "Leave-one-out" method for sensitivity analysis.Conclusion:Two-sample Mendelian randomization supports the causal relationship between rheumatoid arthritis and increased risk of T2D.