Genetic influences on alcohol flushing in East Asian populations
<p><strong>Background</strong> Although it is known that variation in the <i>aldehyde dehydrogenase 2</i> (<i>ALDH2</i>) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Internet publication |
| Language: | English |
| Published: |
Cold Spring Harbor Laboratory
2023
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| _version_ | 1797111493770084352 |
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| author | Cho, Y Lin, K Lee, S-H Yu, C Valle, DS Avery, D Lv, J Jung, K Li, L Smith, GD Chen, Z Millwood, I Hemani, G Walters, R |
| author2 | China Kadoorie Biobank Collaborative Group |
| author_facet | China Kadoorie Biobank Collaborative Group Cho, Y Lin, K Lee, S-H Yu, C Valle, DS Avery, D Lv, J Jung, K Li, L Smith, GD Chen, Z Millwood, I Hemani, G Walters, R |
| author_sort | Cho, Y |
| collection | OXFORD |
| description | <p><strong>Background</strong> Although it is known that variation in the <i>aldehyde dehydrogenase 2</i> (<i>ALDH2</i>) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.</p>
<p><strong>Methods</strong> 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.</p>
<p><strong>Results</strong> We identified variants in the region of <i>ALDH2</i> strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (<i>ADH1B</i>) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (<i>ALDH2</i>-rs671 and <i>ADH1B</i>-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).</p>
<p><strong>Conclusion</strong> This study confirms that <i>ALDH2</i>-rs671 and <i>ADH1B</i>-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.</p>
<p><strong>Trial registration</strong> This study only used secondary data.</p> |
| first_indexed | 2024-03-07T08:11:12Z |
| format | Internet publication |
| id | oxford-uuid:7d0b7581-6838-474d-b887-c7e62408be23 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:11:12Z |
| publishDate | 2023 |
| publisher | Cold Spring Harbor Laboratory |
| record_format | dspace |
| spelling | oxford-uuid:7d0b7581-6838-474d-b887-c7e62408be232023-11-23T08:10:12ZGenetic influences on alcohol flushing in East Asian populationsInternet publicationhttp://purl.org/coar/resource_type/c_7ad9uuid:7d0b7581-6838-474d-b887-c7e62408be23EnglishSymplectic ElementsCold Spring Harbor Laboratory2023Cho, YLin, KLee, S-HYu, CValle, DSAvery, DLv, JJung, KLi, LSmith, GDChen, ZMillwood, IHemani, GWalters, RChina Kadoorie Biobank Collaborative Group<p><strong>Background</strong> Although it is known that variation in the <i>aldehyde dehydrogenase 2</i> (<i>ALDH2</i>) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.</p> <p><strong>Methods</strong> 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.</p> <p><strong>Results</strong> We identified variants in the region of <i>ALDH2</i> strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (<i>ADH1B</i>) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (<i>ALDH2</i>-rs671 and <i>ADH1B</i>-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).</p> <p><strong>Conclusion</strong> This study confirms that <i>ALDH2</i>-rs671 and <i>ADH1B</i>-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.</p> <p><strong>Trial registration</strong> This study only used secondary data.</p> |
| spellingShingle | Cho, Y Lin, K Lee, S-H Yu, C Valle, DS Avery, D Lv, J Jung, K Li, L Smith, GD Chen, Z Millwood, I Hemani, G Walters, R Genetic influences on alcohol flushing in East Asian populations |
| title | Genetic influences on alcohol flushing in East Asian populations |
| title_full | Genetic influences on alcohol flushing in East Asian populations |
| title_fullStr | Genetic influences on alcohol flushing in East Asian populations |
| title_full_unstemmed | Genetic influences on alcohol flushing in East Asian populations |
| title_short | Genetic influences on alcohol flushing in East Asian populations |
| title_sort | genetic influences on alcohol flushing in east asian populations |
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