Obesity, Type 2 Diabetes, and Lifestyle Factors Associated With Risk of Gallstone Disease

An international team of investigators conducted a Mendelian randomization study to determine if obesity, type 2 diabetes, and lifestyle choices contribute to the risk of developing gallstone disease.

Obesity, type 2 diabetes (T2D), and smoking were found to be causally linked to an increased risk for gallstone disease; in contrast, increased consumption of coffee, but not alcohol, was causally linked to a lower risk for gallstone disease. These findings were reported in a study published in Clinical Gastroenterology and Hepatology.    

A Mendelian randomization study was conducted to determine the causal relation between obesity, T2D, and lifestyle factors (consumption of coffee and alcohol, smoking) and the development of gallstone disease. A set of genetic instruments were chosen at the genome-wide significance threshold (P <5×10-8) from relative wide association studies for body mass index (BMI), waist circumference (with and without adjustment for BMI), T2D, as well as cigarette smoking and consumption of alcohol and coffee. Gallstone disease data were acquired from the UK Biobank (10,520 cases and 350,674 noncases) and the FinnGen consortium (11,675 cases and 121,348 noncases). 

The investigators found odds ratios were 1.63 (95% CI, 1.49-1.79) for one standard deviation (SD) increment in body mass index, 1.81 (95% CI, 1.60-2.05) for one SD increment in waist circumference, 1.13 (95% CI, 1.09-1.17) for one unit increment in the log-odds ratio of T2D, and 1.25 (95% CI, 1.16-1.34) for one SD increment in prevalence of smoking commencement. The link between BMI and T2D continued after mutual adjustment. The researchers discovered that genetically predicted coffee consumption was inversely related to gallstone disease after adjustment for BMI and smoking (odds ratio per 50% increase 0.44; 95% CI, 0.21-0.91). No association was found between alcohol consumption and gallstone disease.

Although the study did not differentiate between cholesterol and pigment gallstones, which differ in etiologies, the researchers determined that genetic susceptibility to obesity, T2D, and cigarette smoking was associated with a greater risk of developing gallstone disease. The researchers found that coffee consumption based on genetic predictability was linked to a decreased risk of gallstone disease; however, they did not identify any association between the consumption of alcohol and gallstones. These findings suggest that preventing gallstone disease may be possible through lifestyle modifications. 

Disclosure:  One of the study authors reported being employed in the pharmaceutical industry.  Please see the original reference for a full list of disclosures.


Yuan S, Gill D, Giovannucci EL, Larsson SC. Obesity, type 2 diabetes, lifestyle factors and risk of gallstone disease: a Mendelian randomization investigation. Clin Gastroenterol Hepatol. Published online January 5, 2021.  doi:10.1016/j.cgh.2020.12.034