Evidence map›Paper›PMID 40811757›Full record

ArticlePLoS genetics2025

Understanding the alcohol harm paradox: A multivariable mendelian randomization approach.

Gemma Sawyer, Hannah Sallis, Marcus Munafò, Liam Mahedy, Jasmine Khouja

Abstract read
In one paragraph

Article in PLoS genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Gemma SawyerMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID https://orcid.org/0000-0003-1185-5744
Hannah SallisMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Marcus MunafòMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Liam MahedyMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID https://orcid.org/0000-0001-5417-6595
Jasmine KhoujaMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID https://orcid.org/0000-0002-7944-2981

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The alcohol harm paradox, whereby low socioeconomic position (SEP) groups experience greater alcohol-related harms at a given level of alcohol consumption, is not yet fully understood. In observational studies, key drivers are correlated and share similar confounding structures. We used multivariable Mendelian randomization (MVMR) to estimate the direct causal effect of alcohol (drinks per week) and education (years of schooling) on multiple health outcomes, accounting for the effect of the other. Previously published genome-wide association summary (GWAS) statistics for drinks per week and years of schooling were used, and outcome summary statistics were generated from individual-level data from UK Biobank (N = 462,818). Inverse variance weighted analyses demonstrated evidence for direct effects of alcohol and education on liver diseases (alcoholic liver disease: alcohol OR = 50.19, 95% CI 19.35 to 130.21 and education OR = 0.27, 95% CI 0.14 to 0.53; other liver diseases: alcohol OR = 1.82, 95% CI 1.12 to 2.94 and education OR = 0.42, 95% CI 0.30 to 0.58), mental and behavioural disorders due to alcohol (alcohol OR = 12.89, 95% CI 7.46 to 22.27 and education OR = 0.51, 95% CI 0.35 to 0.75), and stroke (alcohol OR = 1.94, 95% CI 1.30 to 2.89 and education OR = 0.73, 95% CI 0.55 to 0.97). There was evidence for direct effects of education on depression, anxiety, influenza/pneumonia, and heart disease. In contrast, there was evidence of total (without considering the effect of education), but not direct, effects of alcohol on depression, influenza/pneumonia, epilepsy, and injuries. Although caution is required when interpreting these results, given weak instruments for alcohol, these results provide some evidence that the alcohol harm paradox is partially due to the protective effect of additional years of education. Replication with strong genetic instruments for drinks per week would be necessary to draw causal inferences.

Indexed as

Alcohol DrinkingLiver Diseases, AlcoholicMendelian Randomization AnalysisEducational StatusFemaleGenome-Wide Association StudyHumansMaleUnited Kingdom

Identifiers

PMID40811757
PMCPMC12370186

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.