Rheumatoid arthritis and adverse pregnancy outcomes: a bidirectional two-sample mendelian randomization study

Area of Science:

• Reproductive Medicine
• Rheumatology
• Genetics

Background:

• Observational studies suggest links between rheumatoid arthritis (RA) and adverse pregnancy outcomes (APOs).
• The causal direction of these associations remains unclear.
• Mendelian randomization (MR) can investigate causal relationships using genetic variants.

Purpose of the Study:

• To investigate the potential causal relationship between rheumatoid arthritis and adverse pregnancy outcomes.
• To determine the causal direction using a bidirectional two-sample Mendelian randomization approach.
• To analyze these relationships in European and Asian populations.

Main Methods:

• Bidirectional two-sample Mendelian randomization analysis.
• Utilized summary statistics from genome-wide association studies for RA and APOs.
• Employed inverse-variance weighted (IVW) as the primary method, with cML-MA-BIC as supplementary.
• Sensitivity analyses included MR-Egger, MR-PRESSO, and Cochran Q tests.

Main Results:

• Rheumatoid arthritis was causally associated with increased risk of gestational hypertension, pre-eclampsia, fetal growth restriction, and preterm delivery in the European population.
• No evidence of a causal effect of APOs on rheumatoid arthritis was found in the reverse MR analysis.
• No significant associations were observed between rheumatoid arthritis and APOs in the East Asian population.
• Sensitivity analyses confirmed no heterogeneity or horizontal pleiotropy.

Conclusions:

• This MR study provides genetic evidence for a causal link from rheumatoid arthritis to specific adverse pregnancy outcomes.
• Highlights the need for enhanced prenatal care and early intervention for pregnant women with rheumatoid arthritis.
• Suggests distinct genetic underpinnings for RA-APO relationships across different populations.