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Genetic influences on alcohol flushing in East Asian populations

Authors
 Yoonsu Cho  ;  Kuang Lin  ;  Su-Hyun Lee  ;  Canqing Yu  ;  Dan Schmidt Valle  ;  Daniel Avery  ;  Jun Lv  ;  Keumji Jung  ;  Liming Li  ;  George Davey Smith  ;  China Kadoorie Biobank Collaborative Group  ;  Dianjianyi Sun  ;  Zhengming Chen  ;  Iona Y Millwood  ;  Gibran Hemani  ;  Robin G Walters 
Citation
 BMC GENOMICS, Vol.24(1) : 638, 2023-10 
Journal Title
BMC GENOMICS
Issue Date
2023-10
MeSH
Alcohol Dehydrogenase / genetics ; Alcohol Drinking* / genetics ; Aldehyde Dehydrogenase, Mitochondrial / genetics ; East Asian People* / genetics ; Flushing* / chemically induced ; Genome-Wide Association Study ; Humans ; Male ; Polymorphism, Single Nucleotide
Keywords
ADH1B ; ALDH2 ; Alcohol ; Alcohol flushing ; GWAS ; Heritability ; Mendelian randomization
Abstract
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: 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: 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: 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. © 2023, BioMed Central Ltd., part of Springer Nature.
Files in This Item:
T999202516.pdf Download
DOI
10.1186/s12864-023-09721-7
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jung, Keum Ji(정금지) ORCID logo https://orcid.org/0000-0003-4993-0666
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198316
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