Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Gastroenterology
• Public Health

Background:

• Pancreatitis pathogenesis involves diverse, not fully understood, environmental risk factors.
• This study employed Mendelian randomization (MR) to investigate genetically predicted modifiable risk factors for pancreatitis.

Purpose of the Study:

• To systematically investigate the causal effects of genetically predicted modifiable risk factors on pancreatitis.
• To identify specific risk factors contributing to acute pancreatitis (AP), chronic pancreatitis (CP), and alcohol-induced forms.

Main Methods:

• Utilized genome-wide association study data for 30 exposure factors.
• Employed summary-level statistical data for AP, CP, AAP, and ACP from FinnGen consortia.
• Performed univariable and multivariable Mendelian randomization analyses.

Main Results:

• Genetic predisposition to smoking, cholelithiasis, inflammatory bowel disease (IBD), higher triglycerides, BMI, body fat mass, and waist circumference were linked to increased AP risk.
• Smoking, alcohol consumption, cholelithiasis, autoimmune diseases, IBD, type 2 diabetes, higher serum calcium, triglycerides, and waist-to-hip ratio increased CP risk.
• Alcohol consumption strongly predicted alcohol-induced AP (AAP) and ACP; IBD also linked to AAP, while testosterone, triglycerides, and hip circumference affected ACP.

Conclusions:

• The study provides evidence for complex causal associations between various modifiable factors and pancreatitis.
• Findings offer new insights for potential therapeutic and prevention strategies for pancreatitis.
• Identified specific risk factors like smoking, obesity, alcohol, and metabolic conditions warrant targeted interventions.