Phenome-wide study on alcohol consumption provides genetic evidence for a causal association with multiple diseases and biomarkers
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Date
2026
Authors
Assefa Kassaw, N.
Zhou, A.
Stacey, D.
Mulugeta, A.
Lee, S.H.
Burgess, S.
Hyppӧnen, E.
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Nutrition, Metabolism and Cardiovascular Diseases, 2026; 36(6):104624-1-104624-10
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Nigussie Assefa Kassaw, Ang Zhou, David Stacey, Anwar Mulugeta, Sang Hong Lee, Stephen Burgess, Elina Hyppӧnen
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Abstract
Background and aim: This study investigates genetic evidence for a causal association between alcohol intake and 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 trends (all Pnon-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.
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© 2026 The Authors. Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).