Genetic influences on alcohol flushing in East Asian populations.

Humans Male Alcohol Dehydrogenase / genetics Alcohol Drinking / genetics Aldehyde Dehydrogenase, Mitochondrial / genetics East Asian People / genetics Genome-Wide Association Study Polymorphism, Single Nucleotide Flushing / chemically induced
ADH1B ALDH2 Alcohol Alcohol flushing GWAS Heritability Mendelian randomization

Journal

BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258

Informations de publication

Date de publication:
24 Oct 2023
Historique:
received: 26 05 2023
accepted: 06 10 2023
medline: 30 10 2023
pubmed: 25 10 2023
entrez: 24 10 2023
Statut: epublish

Résumé

Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited. We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake. We identified variants in the region of ALDH2 strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (ADH1B) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (ALDH2-rs671 and ADH1B-rs1229984), which need to be confirmed in larger studies. The estimated SNP-heritability on the liability scale was 13% (S.E. = 4%) for flushing, but the heritability estimate decreased to 6% (S.E. = 4%) when the effects of the lead variants were controlled for. Genetic instrumentation of higher alcohol intake using these variants recapitulated known associations of alcohol intake with hypertension. Using self-reported alcohol flushing as an instrument gave a similar association pattern of higher alcohol intake and cardiovascular disease-related traits (e.g. stroke). This study confirms that ALDH2-rs671 and ADH1B-rs1229984 are associated with alcohol flushing in East Asian populations. Our findings also suggest that self-reported alcohol flushing can be used as an instrumental variable in future studies of alcohol consumption.

Sections du résumé

BACKGROUND BACKGROUND
Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.
METHODS METHODS
We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake.
RESULTS RESULTS
We identified variants in the region of ALDH2 strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (ADH1B) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (ALDH2-rs671 and ADH1B-rs1229984), which need to be confirmed in larger studies. The estimated SNP-heritability on the liability scale was 13% (S.E. = 4%) for flushing, but the heritability estimate decreased to 6% (S.E. = 4%) when the effects of the lead variants were controlled for. Genetic instrumentation of higher alcohol intake using these variants recapitulated known associations of alcohol intake with hypertension. Using self-reported alcohol flushing as an instrument gave a similar association pattern of higher alcohol intake and cardiovascular disease-related traits (e.g. stroke).
CONCLUSION CONCLUSIONS
This study confirms that ALDH2-rs671 and ADH1B-rs1229984 are associated with alcohol flushing in East Asian populations. Our findings also suggest that self-reported alcohol flushing can be used as an instrumental variable in future studies of alcohol consumption.

Identifiants

DOI: 10.1186/s12864-023-09721-7 PMID: 37875790 PMC: PMC10594868
pubmed: 37875790
doi: 10.1186/s12864-023-09721-7
pii: 10.1186/s12864-023-09721-7
pmc: PMC10594868
doi:

Substances chimiques

Alcohol Dehydrogenase EC 1.1.1.1
Aldehyde Dehydrogenase, Mitochondrial EC 1.2.1.3
ALDH2 protein, human EC 1.2.1.3
ADH1B protein, human EC 1.1.1.1

Types de publication

Meta-Analysis Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

638

Subventions

Organisme : Medical Research Council
ID : MC_UU_00032/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 29186
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 208806/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00017/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14135
Pays : United Kingdom

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

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Auteurs

Yoonsu Cho (Y)

Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, UK.

Kuang Lin (K)

Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Su-Hyun Lee (SH)

Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.

Canqing Yu (C)

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, 100191, China.
Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, China.

Dan Schmidt Valle (DS)

Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Daniel Avery (D)

Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Jun Lv (J)

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, 100191, China.
Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, China.

Keumji Jung (K)

Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.

Liming Li (L)

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, 100191, China.
Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, China.

George Davey Smith (GD)

Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, UK.
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Dianjianyi Sun (D)

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, 100191, China.
Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, China.

Zhengming Chen (Z)

Nuffield Department of Population Health, University of Oxford, Oxford, UK.
MRC Population Health Research Unit, University of Oxford, Oxford, UK.

Iona Y Millwood (IY)

Nuffield Department of Population Health, University of Oxford, Oxford, UK. iona.millwood@ndph.ox.ac.uk.
MRC Population Health Research Unit, University of Oxford, Oxford, UK. iona.millwood@ndph.ox.ac.uk.

Gibran Hemani (G)

Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK. g.hemani@bristol.ac.uk.
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, UK. g.hemani@bristol.ac.uk.

Robin G Walters (RG)

Nuffield Department of Population Health, University of Oxford, Oxford, UK. robin.walters@ndph.ox.ac.uk.
MRC Population Health Research Unit, University of Oxford, Oxford, UK. robin.walters@ndph.ox.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genetic influences on alcohol flushing in East...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › NAD (+) and NADP (+) dependent Alcohol oxidoreductases › Alcohol dehydrogenase › Genetic influences on alcohol flushing in East...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement dipsique › Consommation d'alcool › Genetic influences on alcohol flushing in East...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines mitochondriales › Aldehyde dehydrogenase, mitochondrial › Genetic influences on alcohol flushing in East...
questionsmedicales.fr › Personnes › Asiatiques › Peuples d'Asie de l'Est › Genetic influences on alcohol flushing in East...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genetic influences on alcohol flushing in East...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Genetic influences on alcohol flushing in East...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations cutanées › Rougeur de la face › Genetic influences on alcohol flushing in East...