Gastroenterology

Genotype

Mendelian randomization

Gene

Endocrinology

Body mass index

Genome-wide association study

Biology

Internal medicine

Diabetes mellitus

Single-nucleotide polymorphism

Genetic variants

Genetics

Medicine

Odds ratio

Cholesterol

Hepatology

Background and Aims The risk factors of cholelithiasis have not been clearly identified, especially for total cholesterol. Here, we try to identify these causal risk factors. Approach and Results We obtained genetic variants associated with the exposures at the genome‐wide significance ( p &lt; 5 × 10 −8 ) level from corresponding genome‐wide association studies. Summary‐level statistical data for cholelithiasis were obtained from FinnGen and UK Biobank (UKB) consortia. Both univariable and multivariable Mendelian randomization (MR) analyses were conducted to identify causal risk factors of cholelithiasis. Results from FinnGen and UKB were combined using the fixed‐effect model. In FinnGen, the odds of cholelithiasis increased per 1‐SD increase of body mass index (BMI) (OR = 1.631, p = 2.16 × 10 −7 ), together with body fat percentage (OR = 2.108, p = 4.56 × 10 −3 ) and fasting insulin (OR = 2.340, p = 9.09 × 10 −3 ). The odds of cholelithiasis would also increase with lowering of total cholesterol (OR = 0.789...

Insights into modifiable risk factors of cholelithiasis: A Mendelian randomization study