Causal association between rheumatoid arthritis and celiac disease: A bidirectional two-sample mendelian...

Area of Science:

• Genetics
• Epidemiology
• Immunology

Background:

• Observational studies suggest an association between Rheumatoid Arthritis (RA) and Celiac Disease (CD).
• The causal relationship and potential confounding factors remain unclear.
• Bidirectional causal links between RA and CD require robust investigation.

Purpose of the Study:

• To investigate the bidirectional causal relationship between Rheumatoid Arthritis and Celiac Disease.
• To determine if RA genetically predisposes individuals to CD.
• To ascertain if CD genetically predisposes individuals to RA.

Main Methods:

• Utilized a two-sample Mendelian randomization (MR) approach.
• Employed genome-wide association study (GWAS) data for RA (58,284 subjects) and CD (15,283 subjects).
• Applied inverse-variance weighted (IVW) as the primary analysis, supported by weighted-median, weighted mode, MR-PRESSO, and MR-Egger regression for sensitivity.

Main Results:

• A significant causal effect of RA on CD was identified (IVW OR: 1.46, 95% CI: 1.19-1.79, p = 3.21E-04).
• Reverse MR analysis showed no significant causal effect of CD on RA (IVW OR: 1.05, 95% CI: 0.91-1.21, p = 0.499).
• Sensitivity analyses indicated that horizontal pleiotropy was unlikely to bias the findings.

Conclusions:

• Rheumatoid Arthritis causally influences Celiac Disease risk in European populations.
• Celiac Disease does not demonstrate a causal effect on Rheumatoid Arthritis.
• Recommends regular assessment for Celiac Disease indicators in Rheumatoid Arthritis patients.