Phenome-wide study on alcohol consumption provides genetic evidence for a causal association with multiple diseases and biomarkers

Background and AimThis study investigates genetic evidence for a causal association between alcohol intake, 1174 diseases and various biomarkers. Methods and Results A phenome-wide Mendelian randomization (MR) study was conducted using data from 337,463 UK Biobank participants. Five MR methods and sensitivity analyses tested linear associations, while non-linear MR assessed intake-dependent effects.Alcohol consumption was associated with 22 distinct diseases across ten categories. Beyond the strong association between genetically indexed alcohol intake with ‘alcohol-related disorders' (OR per log-unit/week: 7.02, 95% CI: 5.26–9.37), MR analyses suggested robust evidence for increased risks of ‘cerebrovascular diseases' (1.63, 1.20–2.21), 'essential hypertension' (1.34, 1.07–1.67), 'electrolyte imbalance' (1.82, 1.34–2.48), ‘magnesium metabolism disorder' (4.39, 2.06–9.39), 'open wounds of head, neck, and trunk' (2.15, 1.39–3.33), and 'symptoms involving nervous and musculoskeletal systems' (2.16, 1.60–2.91). Suggestive evidence indicated higher risks for 12 diseases, mostly mental and digestive disorders, and lower risks for ‘benign neoplasms of connective and other soft tissue', ‘urinary calculus', and migraines. Seven diseases exhibited non-linear yet monotonic trend (all P non-linearity < 0.05). Alcohol intake was robustly associated with biomarkers including bilirubin, urine sodium, urea, and blood pressure. Conclusion This comprehensive analysis supports alcohol's causal role in multiple diseases and biomarkers, highlighting significant risks with minimal benefits.