Causal Association between Rheumatoid Arthritis with the Increased Risk of Type 2 Diabetes: A Mendelian Randomization Analysis
10.4078/jrd.2019.26.2.131
- Author:
Young Ho LEE
1
;
Gwan Gyu SONG
Author Information
1. Department of Rheumatology, Korea University College of Medicine, Seoul, Korea. lyhcgh@korea.ac.kr
- Publication Type:Meta-Analysis
- Keywords:
Rheumatoid arthritis;
Type 2 diabetes;
Mendelian randomization
- MeSH:
Arthritis, Rheumatoid;
Bias (Epidemiology);
Dataset;
Genome-Wide Association Study;
Mendelian Randomization Analysis;
Methods;
Population Characteristics;
Random Allocation
- From:Journal of Rheumatic Diseases
2019;26(2):131-136
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVE: This study aimed to examine whether rheumatoid arthritis (RA) is causally associated with type 2 diabetes (T2D). METHODS: 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. RESULTS: 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). CONCLUSION: MR analysis supports that RA may be causally associated with an increased risk of T2D.
