ArticleAlcohol and alcoholism (Oxford, Oxfordshire)
Rare ADH variant constellations are specific for alcohol dependence.
Article in Alcohol and alcoholism (Oxford, Oxfordshire). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- A New Genomewide Association Meta-Analysis of Alcohol Dependence.Alcoholism, clinical and experimental research · 2015Pooled it
- Genome-wide association discoveries of alcohol dependence.The American journal on addictionsPooled it
- Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism.Human genetics · 2013Trial
- Pleiotropic Association of CACNA1C Variants With Neuropsychiatric Disorders.Schizophrenia bulletin · 2023Article
- Association of ADH7 Gene Polymorphism with Schizophrenia in the Han Population of Northern China: a Case-Control Study.Journal of molecular neuroscience : MN · 2020Article
- Diverse types of genomic evidence converge on alcohol use disorder risk genes.Journal of medical genetics · 2020Article
- Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.Translational psychiatry · 2019Article
- Deep Sequencing of 71 Candidate Genes to Characterize Variation Associated with Alcohol Dependence.Alcoholism, clinical and experimental research · 2017Article
- Significant association between rare IPO11-HTR1A variants and attention deficit hyperactivity disorder in Caucasians.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2015Article
- Drosophila and Caenorhabditis elegans as Discovery Platforms for Genes Involved in Human Alcohol Use Disorder.Alcoholism, clinical and experimental research · 2015Review
- Protective variant associated with alcohol dependence in a Mexican American cohort.BMC medical genetics · 2014Article
- Association and ancestry analysis of sequence variants in ADH and ALDH using alcohol-related phenotypes in a Native American community sample.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2014Article
- Sex chromosome-wide association analysis suggested male-specific risk genes for alcohol dependence.Psychiatric genetics · 2013Article
- Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent.Pharmacogenetics and genomics · 2013Article
- Exome-wide association study of replicable nonsynonymous variants conferring risk for alcohol dependence.Journal of studies on alcohol and drugs · 2013Article
- NKAIN1-SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent.Drug and alcohol dependence · 2013Article
- Genome-wide significant association signals in IPO11-HTR1A region specific for alcohol and nicotine codependence.Alcoholism, clinical and experimental research · 2013Article
- Genetic factors for alcohol dependence and schizophrenia: common and rare variants.Austin journal of drug abuse and addictionArticle
- Common PTP4A1-PHF3-EYS variants are specific for alcohol dependence.The American journal on addictionsArticle
- Alcoholic liver disease: a synopsis of the Charles Lieber's Memorial Symposia 2009-2012.Alcohol and alcoholism (Oxford, Oxfordshire)Article
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
aimsSome of the well-known functional alcohol dehydrogenase (ADH) gene variants (e.g. ADH1B*2, ADH1B*3 and ADH1C*2) that significantly affect the risk of alcohol dependence are rare variants in most populations. In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF) <0.05] and alcohol dependence, with several other neuropsychiatric and neurological disorders as reference.
methodsA total of 49,358 subjects in 22 independent cohorts with 11 different neuropsychiatric and neurological disorders were analyzed, including 3 cohorts with alcohol dependence. The entire ADH gene cluster (ADH7-ADH1C-ADH1B-ADH1A-ADH6-ADH4-ADH5 at Chr4) was imputed in all samples using the same reference panels that included whole-genome sequencing data. We stringently cleaned the phenotype and genotype data to obtain a total of 870 single nucleotide polymorphisms with 0< MAF <0.05 for association analysis.
resultsWe found that a rare variant constellation across the entire ADH gene cluster was significantly associated with alcohol dependence in European-Americans (Fp1: simulated global P = 0.045), European-Australians (Fp5: global P = 0.027; collapsing: P = 0.038) and African-Americans (Fp5: global P = 0.050; collapsing: P = 0.038), but not with any other neuropsychiatric disease. Association signals in this region came principally from ADH6, ADH7, ADH1B and ADH1C. In particular, a rare ADH6 variant constellation showed a replicable association with alcohol dependence across these three independent cohorts. No individual rare variants were statistically significantly associated with any disease examined after group- and region-wide correction for multiple comparisons.
conclusionWe conclude that rare ADH variants are specific for alcohol dependence. The ADH gene cluster may harbor a causal variant(s) for alcohol dependence.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.