Association between 23 drugs and inflammatory bowel disease: a two-sample Mendelian randomization study

Area of Science:

• Genetics
• Pharmacology
• Gastroenterology

Background:

• Inflammatory bowel disease (IBD) involves chronic gastrointestinal inflammation with poorly understood causes.
• Current treatments for IBD focus on disease induction and remission, necessitating exploration of novel therapeutic options.
• Mendelian randomization (MR) analysis is a valuable tool for investigating causal relationships between drugs and diseases.

Purpose of the Study:

• To investigate the potential causal relationship between 23 approved drugs and the risk of developing inflammatory bowel disease (IBD).
• To explore existing medications as potential therapeutic options for IBD prevention and management.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis was conducted using publicly available genome-wide association study (GWAS) statistics.
• The inverse variance weighting (IVW) method was the primary analysis approach, supported by weighted median, MR Egger regression, and simple/weighted models.
• Cochran's Q statistic and the MR-Egger test were used to assess heterogeneity and pleiotropy.

Main Results:

• Immunosuppressants showed a negative causal association with IBD risk (OR=0.7389, p=0.0046), also observed for ulcerative colitis (UC) and Crohn's disease (CD).
• Diabetes medications demonstrated a potential risk reduction for IBD (OR=0.9266, p=0.0058) and UC (OR=0.9020, p=0.0046).
• Salicylic acid and derivatives were associated with increased IBD risk (OR=1.2737, p=0.0345), while beta-blockers were linked to increased UC risk (OR=1.1893, p=0.0046).

Conclusions:

• Immunosuppressants may mitigate the risk of IBD, showing consistent effects in UC and CD subtypes.
• Diabetes medications show promise in reducing IBD risk, particularly for UC.
• Salicylic acid derivatives and beta-blockers warrant further investigation regarding their potential to increase IBD and UC risk, respectively.