Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach
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BACKGROUND: Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour. METHODS AND FINDINGS: We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66-3.55, p = 4.8 x 10(-6)) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17-2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39-9.49, p = 1.1 x 10(-12)) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18-6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes. CONCLUSIONS: These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
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The dose-response association between alcohol and blood pressure may differ between men (linear) and women (J shaped) and can be modified by metabolic genes.
“The dose-response association may differ between men (linear) and women (J shaped)164 and can be modified by metabolic genes.163”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [163]
Alcohol intake has been linked to increases in blood pressure and the risk for developing hypertension.
“Alcohol intake has been linked to increases in BP and the risk for developing hypertension.162–164”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [163]
A DASH-style eating pattern, alcohol restriction to <10 g/d (women) and <20 g/d (men), and a variety of other dietary modifications can each yield significant reductions in BP among patients with hypertension.
“A DASH-style eating pattern,174,175 alcohol restriction to <10 g/d (women) and <20 g/d (men),162–165 and a variety of other dietary modifications174 can each yield significant reductions in BP among patients with hypertension.”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [163]
If the multivariable Mendelian randomization conditions are met, the estimates obtained will be a direct effect of each exposure included on the outcome, given the other exposures included in the estimation.
“If the above conditions are met, the estimates obtained from multivariable MR will be a direct effect of each exposure included on the outcome, given the other exposures included in the estimation.74”
From Mendelian randomization (2022) · cites this paper as [74]
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- Authors
- Chen, L., Davey Smith, G., Harbord, R. M., & Lewis, S. J.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Lewis, Sarah J
- Venue
- PLoS Medicine
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-03-04
- Volume
- 5
- Issue
- 3
- Pages
- e52
- ISSN
- 1549-1277 (ISSN-L)
- 1549-1676
- PMC
- PMC2265305
- OpenAlex
- W2097040757
- Cited by
- 314
- References
- 32
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 18 · 2023: 13 · 2022: 15 · 2021: 17 · 2020: 27 · 2019: 17 · 2018: 21 · 2017: 16 · 2016: 19 · 2015: 15 · 2014: 20 · 2013: 22 · 2012: 25
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- alcohol consumption, blood pressure, hypertension, ALDH2, ALDH2 polymorphism, genetic susceptibility, alcohol metabolism, systolic blood pressure
- MeSH terms
- Alcohol Dehydrogenase, Alcohol Drinking, Blood Pressure, Humans, Hypertension, Male, Genetic Predisposition to Disease
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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