The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722
Operating characteristics of a rank correlation test for publication bias
Begg, C. B., & Mazumdar, M. (1994) · Biometrics · doi:10.2307/2533446 · Cited by 16,955
Davey Smith, G., & Ebrahim, S. (2003) · International Journal of Epidemiology · doi:10.1093/ije/dyg070 · Cited by 5,882
BOSRON, W. F., & Li, T. (1986) · Hepatology · doi:10.1002/hep.1840060330 · Cited by 569
Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals.
Yoshida, A., Huang, I. Y., & Ikawa, M. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.1.258 · Cited by 456
Alcohol Consumption and the Incidence of Hypertension
Fuchs, F. D., Chambless, L. E., Whelton, P. K., Nieto, F. J., & HEISS, G. M. (2001) · Hypertension · doi:10.1161/01.hyp.37.5.1242 · Cited by 409
Alcohol and blood pressure: the INTERSALT study
Marmot, M. G., Elliott, P., Shipley, M. J., Dyer, A. R., Ueshima, H., Beevers, D. G., Stamler, R., Kesteloot, H., Rose, G., & Stamler, J. (1994) · BMJ · doi:10.1136/bmj.308.6939.1263 · Cited by 353
Acetaldehyde Metabolism in Different Aldehyde Dehydrogenase‐2 Genotypes
Enomoto, N., Takase, S., Yasuhara, M., & Takada, A. (1991) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1991.tb00532.x · Cited by 266
Lewis, S. J., & Smith, G. D. (2005) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-05-0196 · Cited by 234
Self-citationThe Role of Acetaldehyde in the Actions of Alcohol (Update 2000)
Eriksson, C. J. P. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1097/00000374-200105051-00005 · Cited by 205
The appetizing effect of an apéritif in overweight and normal-weight humans
Westerterp‐Plantenga, M. S., & Verwegen, C. R. T. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.2.205 · Cited by 155
Alcohol Consumption and Risk for Coronary Heart Disease among Men with Hypertension
Beulens, J. W. J., Rimm, E. B., Ascherio, A., Spiegelman, D. L., Hendriks, H., & Mukamal, K. J. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-1-200701020-00004 · Cited by 133
Lukasiewicz, E., Mennen, L. I., Bertrais, S., Arnault, N., Preziosi, P., Galan, P., & Herçberg, S. (2005) · Public Health Nutrition · doi:10.1079/phn2004680 · Cited by 130
Sakurai, M., Miura, K., Takamura, T., Ota, T., Ishizaki, M., Morikawa, Y., Kido, T., Naruse, Y., & Nakagawa, H. (2006) · Hypertension Research · doi:10.1291/hypres.29.75 · Cited by 126
Econometrics: A Modern Introduction
Murray, M. P. (2005) · Cited by 97
Aldehyde Dehydrogenase 2 Plays a Role in the Bioactivation of Nitroglycerin in Humans
Mackenzie, I. S., Maki-Petaja, K. M., McEniery, C. M., Bao, Y. P., Wallace, S. M. L., Cheriyan, J., Monteith, S., Brown, M. J., & Wilkinson, I. B. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000179599.71086.89 · Cited by 97
Takagi, S., Baba, S., Iwai, N., FUKUDA, M., Katsuya, T., Higaki, J., Mannami, T., Ogata, J., Goto, Y., & Ogihara, T. (2001) · Hypertension Research · doi:10.1291/hypres.24.365 · Cited by 95
Dose-dependent biphasic effect of ethanol on 24-h blood pressure in normotensive subjects
Rosito, G. A. (1999) · American Journal of Hypertension · doi:10.1016/s0895-7061(98)00237-4 · Cited by 91
Amamoto, K., Okamura, T., Tamaki, S., Kita, Y., Tsujita, Y., Kadowaki, T., Nakamura, Y., & Ueshima, H. (2002) · Hypertension Research · doi:10.1291/hypres.25.857 · Cited by 78
Hashimoto, Y., Nakayama, T., Futamura, A., Omura, M., Nakarai, H., & Nakahara, K. (2002) · Clinical Chemistry · doi:10.1093/clinchem/48.7.1043 · Cited by 67
The role of acetaldehyde in the actions of alcohol
Cjp, E. (2001) · STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) · Cited by 66
Folate supplementation and cardiovascular disease
Smith, G. D., & Ebrahim, S. B. J. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67676-3 · Cited by 63
Genetic analysis of 22 candidate genes for hypertension in the Japanese population
Iwai, N., Tago, N., Yasui, N., Kokubo, Y., Inamoto, N., Tomoike, H., & Shioji, K. (2004) · Journal of Hypertension · doi:10.1097/00004872-200406000-00012 · Cited by 56
Pittler, M. H., White, A. R., Stevinson, C. D., & Ernst, E. (2003) · Europe PMC (PubMed Central) · Cited by 42
Polymorphism in ALDH2-genotype in Japanese men and the alcohol-blood pressure relationship*
Tsuritani, I., Ikai, E., Date, T., Suzuki, Y., Ishizaki, M., & Yamada, Y. (1995) · American Journal of Hypertension · doi:10.1016/0895-7061(95)00222-b · Cited by 41
Saito, K., Yokoyama, A., Yoshiike, N., Date, C., Yamamoto, A., Muramatsu, M., & Tanaka, H. (2003) · Journal of Hypertension · doi:10.1097/00004872-200306000-00009 · Cited by 40
Nishimura, F. T., Fukunaga, T., Kajiura, H., Umeno, K., Takakura, H., Ono, T., & Nishijo, H. (2002) · Autonomic Neuroscience · doi:10.1016/s1566-0702(02)00206-0 · Cited by 39
Alcohol Consumption and Blood Pressure in the 1982 Maryland Hypertension Survey
Moore, R. D., Levine, D. M., Southard, J. G., Entwise, G., & Shapiro, S. (1990) · American Journal of Hypertension · doi:10.1093/ajh/3.1.1 · Cited by 38
Okayama, A., Ueshima, H., Yamakawa, M., & Kita, Y. (1994) · PubMed · Cited by 37
Changes in Blood Pressure and Autonomic Reflexes Following Regular, Moderate Alcohol Consumption
Howes, L. G., & Reid, J. L. (1986) · Journal of Hypertension · doi:10.1097/00004872-198608000-00005 · Cited by 36
Patel, R., Lawlor, D. A., Whincup, P. H., Montaner, D. A., Papacosta, O., Brindle, P., & Ebrahim, S. B. J. (2006) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1002064 · Cited by 22
Yamada, Y., Imai, T., Ishizaki, M., & Honda, R. (2005) · Journal of Human Genetics · doi:10.1007/s10038-005-0330-0 · Cited by 11
Research works printed but not linked: 29
- Marmot, 1994, BMJ, 308, 1263
- Patel, 2006, J Hum Hypertens, 20, 733
- Fuchs, 2001, Hypertension, 37, 1242
- Moore, 1990, Am J Hypertens, 3, 1
- Davey Smith, 2003, Int J Epidemiol, 32, 1
- Bosron, 1986, Hepatology, 6, 502
- Yoshida, 1984, Proc Natl Acad Sci U S A, 81, 258
- Enomoto, 1991, Alcohol Clin Exp Res, 15, 141
- Lewis, 2005, Cancer Epidemiol Biomarkers Prev, 14, 1967
- Pittler, 2003, CMAJ, 169, 1269
- Mackenzie, 2005, Arterioscler Thromb Vasc Biol, 25, 1891
- Hashimoto, 2002, Clin Chem, 48, 1043
- Okayama, 1994, J Hum Hypertens, 8, 205
- Egger, 1997, BMJ, 315, 629
- Begg, 1994, Biometrics, 50, 1088
- Amamoto, 2002, Hypertens Res, 25, 857
- Takagi, 2001, Hypertens Res, 24, 365
- Tsuritani, 1995, Am J Hypertens, 8, 1053
- Howes, 1986, J Hypertens, 4, 421
- Rosito, 1999, Am J Hypertens, 12, 236
- Beulens, 2007, Ann Intern Med, 146, 10
- Westerterp-Plantenga, 1999, Am J Clin Nutr, 69, 205
- Lukasiewicz, 2005, Public Health Nutr, 8, 315
- Sakurai, 2006, Hypertens Res, 29, 75
- Eriksson, 2001, Alcohol Clin Exp Res, 25, 15S
- Saito, 2003, J Hypertens, 21, 1097
- Yamada, 2006, J Hum Genet, 51, 104
- Davey Smith, 2005, Lancet, 366, 1679
- Iwai, 2004, J Hypertens, 22, 1119
Cited by
Sorted by citations
Forouzanfar, M. H., Afshin, A., Alexander, L. T., Anderson, H. R., Bhutta, Z. A., Biryukov, S., Brauer, M., Burnett, R., Cercy, K., Charlson, F. J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31679-8 · Cited by 7,698
Mendelian randomization: genetic anchors for causal inference in epidemiological studies
Davey Smith, G., & Hemani, G. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu328 · Cited by 4,677
Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians
Davies, N. M., Holmes, M. V., & Davey Smith, G. (2018) · BMJ · doi:10.1136/bmj.k601 · Cited by 4,404
Sanderson, E., Glymour, M. M., Holmes, M. V., Kang, H., Morrison, J., Munafò, M. R., Palmer, T., Schooling, C. M., Wallace, C., Zhao, Q., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00092-5 · Cited by 2,229
Guidelines for performing Mendelian randomization investigations
Burgess, S., Smith, G. D., Davies, N. M., Dudbridge, F., Gill, D., Glymour, M. M., Hartwig, F. P., Holmes, M. V., Minelli, C., Relton, C. L., et al. (2019) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15555.1 · Cited by 1,828
Metadata
- 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
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
