Causal Relationship Between Cataracts and Gastrointestinal Diseases: A Two-Sample Mendelian Randomization Study

Area of Science:

• Ophthalmology and Genetics
• Gastroenterology and Epidemiology

Background:

• Cataracts are a leading cause of blindness globally.
• Previous associations between cataracts and gastrointestinal diseases lack established causality.
• Systemic conditions are increasingly linked to cataract development.

Purpose of the Study:

• To investigate the causal relationship between cataracts and 23 gastrointestinal diseases using Mendelian randomization (MR).
• To explore potential mediating roles of plasma metabolites in the GERD-cataract pathway.

Main Methods:

• Genome-wide association study (GWAS) datasets for cataracts and 23 gastrointestinal diseases in European populations were utilized.
• Multivariable Mendelian randomization (MR) was employed to assess causality and adjust for lipid-related confounders.
• A two-step MR analysis investigated the mediating role of 1400 plasma metabolites.

Main Results:

• Gastroesophageal reflux disease (GERD) and celiac disease were causally associated with increased cataract risk.
• GERD showed a specific link to senile cataract; celiac disease showed suggestive links to senile, drug-induced, and other cataract types.
• 1-linoleoyl-GPE (18:2) was identified as a potential mediator in the GERD-cataract pathway.

Conclusions:

• This study establishes causal links between specific gastrointestinal diseases and cataracts.
• Findings provide novel insights into the biological mechanisms connecting these conditions.
• Results support targeted screening and early intervention for at-risk populations.