J Rheum Dis.  2019 Apr;26(2):131-136. 10.4078/jrd.2019.26.2.131.

Causal Association between Rheumatoid Arthritis with the Increased Risk of Type 2 Diabetes: A Mendelian Randomization Analysis

  • 1Department of Rheumatology, Korea University College of Medicine, Seoul, Korea. lyhcgh@korea.ac.kr


This study aimed to examine whether rheumatoid arthritis (RA) is causally associated with type 2 diabetes (T2D).
We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We used the publicly available summary statistics datasets from a genome-wide association studies (GWAS) meta-analysis of 5,539 autoantibody-positive individuals with RA and 20,169 controls of European descent, and a GWAS dataset of 10,247 individuals with T2D and 53,924 controls, overwhelmingly of European descent as outcomes.
We selected 10 single-nucleotide polymorphisms from GWAS data on RA as instrumental variables to improve the inference. The IVW method supported a causal association between RA and T2D (β=0.044, standard error [SE]=0.022, p=0.047). The MR-Egger analysis showed a causal association between RA and T2D (β=0.093, SE=0.033, p=0.023). In addition, the weighted median approach supported a causal association between RA and T2D (β=0.056, SE=0.025, p=0.028). The association between RA and T2D was consistently observed using IVW, MR Egger, and weighted median methods. Cochran's Q test indicated no evidence of heterogeneity between instrumental variable estimates based on individual variants and MR-Egger regression revealed that directional pleiotropy was unlikely to have biased the results (intercept=−0.030; p=0.101).
MR analysis supports that RA may be causally associated with an increased risk of T2D.


Rheumatoid arthritis; Type 2 diabetes; Mendelian randomization

MeSH Terms

Arthritis, Rheumatoid*
Bias (Epidemiology)
Genome-Wide Association Study
Mendelian Randomization Analysis*
Population Characteristics
Random Allocation


  • Figure 1. Forest plot of the causal effects of rheumatoid arthri-tis-associated single-nucleotide polymorphisms on type 2 diabetes. MR: Mendelian randomization, IVW: inverse-variance weighted.

  • Figure 2. Scatter plots of the genetic associations of rheumatoid arthritis against those of type 2 diabetes. The slopes of each line represent the causal association for each method. Blue line represents the inverse-variance weighted estimate, green line represents the weighted median estimate, and dark blue line represents the MR-Egger estimate. SNP: single-nucleotide polymorphism.


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