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Understanding the alcohol harm paradox: A multivariable mendelian randomization approach.
Gemma Sawyer1, Hannah Sallis1,2, Marcus Munafò1,3
1MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Plos Genetics
|August 14, 2025
Summary
Low socioeconomic position groups face greater alcohol harms. This study suggests more education may offer a protective effect, partially explaining the alcohol harm paradox.
Area of Science:
- Genetics and Epidemiology
- Public Health
Background:
- The alcohol harm paradox highlights increased alcohol-related harm in lower socioeconomic position (SEP) groups.
- Observational studies face challenges due to correlated drivers and confounding factors.
Purpose of the Study:
- To estimate the direct causal effects of alcohol consumption and education on various health outcomes using multivariable Mendelian randomization (MVMR).
- To investigate the role of education in mitigating alcohol-related harms and understand the alcohol harm paradox.
Main Methods:
- Utilized genome-wide association study (GWAS) summary statistics for alcohol consumption (drinks per week) and education (years of schooling).
- Employed multivariable Mendelian randomization (MVMR) to disentangle direct causal effects.
- Analyzed individual-level data from UK Biobank (N=462,818) for outcome statistics.
Main Results:
- Direct causal effects of alcohol consumption were found for liver diseases, alcohol-related mental and behavioral disorders, and stroke.
- Direct causal effects of education were observed for liver diseases, alcohol-related disorders, stroke, depression, anxiety, influenza/pneumonia, and heart disease.
- Total effects of alcohol were evident for depression, influenza/pneumonia, epilepsy, and injuries, but direct effects were not significant.
Conclusions:
- Additional years of education appear to have a protective effect, partially explaining the alcohol harm paradox.
- While results suggest education's protective role, caution is advised due to weak genetic instruments for alcohol consumption.
- Further research with stronger genetic instruments for alcohol is necessary to confirm causal inferences.
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