Addictive behavior and incident gallstone disease: A dose–response meta-analysis and Mendelian randomization study

Abstract

BackgroundPrevious studies have suggested associations between addictive behavior and gallstone disease (GSD) risk, yet conflicting results exist. It also remains unclear whether this association is causal or due to confounding or reverse associations. The present study aims to systematically analyze the epidemiological evidence for these associations, as well as estimate the potential causal relationships using Mendelian randomization (MR).MethodsWe analyzed four common addictive behaviors, including cigarette smoking, alcohol intake, coffee, and tea consumption (N = 126,906–4,584,729 participants) in this meta-analysis based on longitudinal studies. The two-sample MR was conducted using summary data from genome-wide associations with European ancestry (up to 1.2 million individuals).ResultsAn observational association of GSD risk was identified for smoking [RR: 1.17 (95% CI: 1.06–1.29)], drinking alcohol [0.84 (0.78–0.91)], consuming coffee [0.86 (0.79–0.93)], and tea [1.08 (1.04–1.12)]. Also, there was a linear relationship between smoking (pack-years), alcohol drinking (days per week), coffee consumption (cups per day), and GSD risk. Our MRs supported a causality of GSD incidence with lifetime smoking [1.008 (1.003–1.013), P = 0.001], current smoking [1.007 (1.002–1.011), P = 0.004], problematic alcohol use (PAU) [1.014 (1.001–1.026), P = 0.029], decaffeinated coffee intake (1.127 [1.043–1.217], P = 0.002), as well as caffeine-metabolism [0.997 (0.995–0.999), P = 0.013], and tea consumption [0.990 (0.982–0.997), P = 0.008], respectively.ConclusionOur study suggests cigarette smoking, alcohol abuse, and decaffeinated coffee are causal risk factors for GSD, whereas tea consumption can decrease the risk of gallstones due to the effect of caffeine metabolism or polyphenol intake.

The Association Between Cotinine-Verified Smoking Status and Risk of Gallstones: A Cohort Study

“…Another Mendelian randomization study also supported a causality of gallstone disease incidence with lifetime smoking (OR=1.008; 95%CI: 1.003-1.013) and current smoking (OR=1.007; 95%CI: 1.002-1.011) [25]. In contrast, some other studies have failed to establish an association between smoking and developing gallstones.…”

Exploration of the Causal Association Between Behavioral Risk Factors and Gallstone Disease Development in Two European Ancestry Populations

“…A similar study assessed the risk of gallstone disease among a sample of the UK Biobank (including 10520 cases of gallstone disease), and a sample from the FinnGen consortium (including a sample of 11675 gallstone disease) according to the estimated genetic risk of type 2 diabetes, obesity, and specific lifestyle factors (cigarette smoking, and alcohol and coffee consumption). The study identified an increased risk of gallstone disease with BMI, waist circumference, diabetes, and smoking initiation, and a protective effect of coffee consumption against gallstone disease development [ 18 ]. Our investigation also identified a similar association between elevated BMI levels and smoking initiation and the increased risk of gallstone disease, and a protective effect of coffee intake against the development of gallstone disease.…”