Associations and interactions between SNPs in the alcohol metabolizing genes and alcoholism phenotypes in European Americans.
- Authors
- Sherva, Richard; Rice, John P; Neuman, Rosalind J; Rochberg, Nanette; Saccone, Nancy L; Bierut, Laura J
- Year
- 2009
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 19298322
- DOI
- 10.1111/j.1530-0277.2009.00904.x
- PMCID
- PMC2892966
BACKGROUND: Alcohol dependence is a major cause of morbidity and mortality worldwide and has a strong familial component. Several linkage and association studies have identified chromosomal regions and/or genes that affect alcohol consumption, notably in genes involved in the 2-stage pathway of alcohol metabolism. METHODS: Here, we use multiple regression models to test for associations and interactions between 2 alcohol-related phenotypes and SNPs in 17 genes involved in alcohol metabolism in a sample of 1,588 European American subjects. RESULTS: The strongest evidence for association after correcting for multiple testing was between rs1229984, a nonsynonymous coding SNP in ADH1B, and DSM-IV symptom count (p = 0.0003). This SNP was also associated with maximum number of drinks in 24 hours (p = 0.0004). Each minor allele at this SNP predicts 45% fewer DSM-IV symptoms and 18% fewer max drinks. Another SNP in a splice site in ALDH1A1 (rs8187974) showed evidence for association with both phenotypes as well (p = 0.02 and 0.004, respectively), but neither association was significant after accounting for multiple testing. Minor alleles at this SNP predict greater alcohol consumption. In addition, pairwise interactions were observed between SNPs in several genes (p = 0.00002). CONCLUSIONS: We replicated the large effect of rs1229984 on alcohol behavior, and although not common (MAF = 4%), this polymorphism may be highly relevant from a public health perspective in European Americans. Another SNP, rs8187974, may also affect alcohol behavior but requires replication. Also, interactions between polymorphisms in genes involved in alcohol metabolism are likely determinants of the parameters that ultimately affect alcohol consumption.
No figures extracted from this document.
No entities extracted from this document yet.
No uploaded files.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Genomic imputation of ancient Asian populations contrasts local adaptation in pre- and post-agricultural Japan. | Cooke NP et al. | — | 2024 | → |
| Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review. | Tsermpini EE et al. | — | 2022 | → |
| <i>ALDH1A1</i> Genetic Variations May Modulate Risk of Parkinson's Disease in Han Chinese Population. | Fan HH et al. | — | 2021 | → |
| Ancient genome-wide DNA from France highlights the complexity of interactions between Mesolithic hunter-gatherers and Neolithic farmers. | Rivollat M et al. | — | 2020 | → |
| GABA uptake transporters support dopamine release in dorsal striatum with maladaptive downregulation in a parkinsonism model. | Roberts BM et al. | — | 2020 | → |
| The causal web of foetal alcohol spectrum disorders: a review and causal diagram. | McQuire C et al. | — | 2020 | → |
| Neuroblastoma in relation to joint effects of vitamin A and maternal and offspring variants in vitamin A-related genes: A report of the Children's Oncology Group. | Mazul AL et al. | — | 2019 | → |
| Alcohol Dehydrogenases, Aldehyde Dehydrogenases, and Alcohol Use Disorders: A Critical Review. | Edenberg HJ et al. | — | 2018 | → |
| Alcohol Metabolizing Polygenic Risk for Alcohol Consumption in European American College Students. | Thomas NS et al. | — | 2018 | → |
| Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors. | Jiao J et al. | — | 2018 | → |
| Alcohol metabolism and oesophageal cancer: a systematic review of the evidence. | Matejcic M et al. | — | 2017 | → |
| Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease. | Sookoian S et al. | — | 2016 | → |
| Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons. | Kim JI et al. | — | 2015 | → |
| Application of mass spectrometry-based metabolomics in identification of early noninvasive biomarkers of alcohol-induced liver disease using mouse model. | Manna SK et al. | — | 2015 | → |
| Candidate gene study for smoking, alcohol use, and body weight in a sample of pregnant women. | Wehby GL et al. | — | 2015 | → |
| XRCC5 as a risk gene for alcohol dependence: evidence from a genome-wide gene-set-based analysis and follow-up studies in Drosophila and humans. | Juraeva D et al. | — | 2015 | → |
| Alcohol Exposure <i>In Utero</i> and Child Academic Achievement. | von Hinke Kessler Scholder S et al. | — | 2014 | → |
| Genetic influences on response to alcohol and response to pharmacotherapies for alcoholism. | Enoch MA | — | 2014 | → |
| Methylation of a CpG site near the ALDH1A2 gene is associated with loss of control over drinking and related phenotypes. | Harlaar N et al. | — | 2014 | → |
| Association of the ALDH1A1*2 promoter polymorphism with alcohol phenotypes in young adults with or without ALDH2*2. | Otto JM et al. | — | 2013 | → |
| Genetic influences on the development of alcoholism. | Enoch MA | — | 2013 | → |
| Genetic instrumental variable studies of effects of prenatal risk factors. | Wehby GL et al. | — | 2013 | → |
| The Impact of ADH1B Alleles and Educational Status on Levels and Modes of Alcohol Consumption in Russian Male Individuals. | Borinskaya SA et al. | — | 2013 | → |
| ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry. | Bierut LJ et al. | — | 2012 | → |
| Further clarification of the contribution of the ADH1C gene to vulnerability of alcoholism and selected liver diseases. | Li D et al. | — | 2012 | → |
| Genes encoding enzymes involved in ethanol metabolism. | Hurley TD et al. | — | 2012 | → |
| The CHRNA5/A3/B4 gene cluster and tobacco, alcohol, cannabis, inhalants and other substance use initiation: replication and new findings using mixture analyses. | Lubke GH et al. | — | 2012 | → |
| The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks. | Morozova TV et al. | — | 2012 | → |
| Association of alcohol dehydrogenase genes with alcohol-related phenotypes in a Native American community sample. | Gizer IR et al. | — | 2011 | → |
| Convergent functional genomic studies of ω-3 fatty acids in stress reactivity, bipolar disorder and alcoholism. | Le-Niculescu H et al. | — | 2011 | → |
| Genetic vulnerability and susceptibility to substance dependence. | Bierut LJ | — | 2011 | → |
| Haplotype-based study of the association of alcohol-metabolizing genes with alcohol dependence in four independent populations. | Liu J et al. | — | 2011 | → |
| Strong association of the alcohol dehydrogenase 1B gene (ADH1B) with alcohol dependence and alcohol-induced medical diseases. | Li D et al. | — | 2011 | → |
| UPLC-MS-based urine metabolomics reveals indole-3-lactic acid and phenyllactic acid as conserved biomarkers for alcohol-induced liver disease in the Ppara-null mouse model. | Manna SK et al. | — | 2011 | → |
| ADH1B*2 allele is protective against alcoholism but not chronic liver disease in the Hungarian population. | Toth R et al. | — | 2010 | → |
| A non-synonymous variant in ADH1B is strongly associated with prenatal alcohol use in a European sample of pregnant women. | Zuccolo L et al. | — | 2009 | → |