Causal relationship between inflammatory bowel disease and sex: a Mendelian randomization study

Area of Science:

• Endocrinology
• Gastroenterology
• Genetic Epidemiology

Background:

• Inflammatory Bowel Disease (IBD) is a chronic condition with complex etiology.
• The role of sex hormones in IBD pathogenesis remains incompletely understood.
• Previous studies suggest potential links between sex hormones and IBD, but bidirectional causality is unclear.

Purpose of the Study:

• To investigate the bidirectional causal relationship between key sex hormones and IBD.
• To differentiate the effects of sex hormones on IBD risk between males and females.

Main Methods:

• A two-sample Mendelian randomization (MR) study was conducted using Genome-Wide Association Study (GWAS) data.
• Data included European populations for sex hormone-binding globulin (SHBG), total testosterone, bioavailable testosterone, estradiol, and IBD.
• Various MR methods (IVW, weighted median, weighted mode, MR-Egger) were employed to assess causality.

Main Results:

• No significant causal relationship was found between sex hormones and IBD in women.
• In men, a positive causal correlation was observed between SHBG and IBD (OR=1.22) and testosterone and IBD (OR=1.20).
• IBD was associated with decreased SHBG and testosterone levels in men, indicating a bidirectional effect.

Conclusions:

• Female sex hormones do not appear to causally influence IBD risk.
• Male SHBG and testosterone are positively correlated with IBD risk, and IBD influences these hormone levels in men.
• Sex hormones play distinct roles in IBD pathogenesis, differing between sexes.