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Unraveling time-dependent genetic components underlying alcohol response
Keiko Hikino1, Ikuo Otsuka2, Shunji Oshima3
1Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan.
Summary
This study reveals distinct genetic influences on subjective alcohol response (SR) in Japanese adults. Identifying genetic profiles can help predict individual alcohol reactivity and inform personalized health risk assessments.
Area of Science:
- Pharmacogenetics
- Human Genetics
- Alcohol Metabolism
Background:
- Subjective response to alcohol (SR) is a key phenotype for understanding alcohol use disorders.
- Previous research lacked in-depth analysis linking alcohol reactivity to genetic factors in large cohorts.
- Genetic variants in alcohol metabolism pathways are crucial for individual differences in alcohol response.
Purpose of the Study:
- To quantify the contribution of specific genetic variants to the variability in subjective alcohol response.
- To investigate the relationship between genetic factors (ALDH2, ADH1B, ALDH1B1, ALDH1A1, GCKR) and SR in Japanese individuals.
- To identify distinct clusters of subjective alcohol response profiles and their genetic underpinnings.
Main Methods:
- Utilized an intravenous alcohol clamp technique in 429 healthy Japanese young adults.
- Assessed subjective response to alcohol (SR) using various subscales.
- Applied dimensionality reduction to identify clusters of SR and participants based on genetic factors.
Main Results:
- Identified three distinct clusters of participants and SR profiles, each with unique genetic contributions.
- Participant cluster 1 showed the strongest alcohol response, potentially influenced by ALDH2 and ADH1B allelic status.
- Genotype-phenotype relationships were consistent across participant and subscale clusters, with varying variance explained by genes.
Conclusions:
- The study established a clear genotype-phenotype relationship for subjective alcohol response.
- Distinct genetic profiles influence alcohol reactivity, with ALDH2 and ADH1B playing significant roles.
- This three-cluster classification offers potential for early identification of individuals at health risk due to alcohol consumption.
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