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Literature DB >> 20202923

A genome-wide association study of alcohol dependence.

Laura J Bierut¹, Arpana Agrawal, Kathleen K Bucholz, Kimberly F Doheny, Cathy Laurie, Elizabeth Pugh, Sherri Fisher, Louis Fox, William Howells, Sarah Bertelsen, Anthony L Hinrichs, Laura Almasy, Naomi Breslau, Robert C Culverhouse, Danielle M Dick, Howard J Edenberg, Tatiana Foroud, Richard A Grucza, Dorothy Hatsukami, Victor Hesselbrock, Eric O Johnson, John Kramer, Robert F Krueger, Samuel Kuperman, Michael Lynskey, Karl Mann, Rosalind J Neuman, Markus M Nöthen, John I Nurnberger, Bernice Porjesz, Monika Ridinger, Nancy L Saccone, Scott F Saccone, Marc A Schuckit, Jay A Tischfield, Jen C Wang, Marcella Rietschel, Alison M Goate, John P Rice.

Abstract

Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10(-5), but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2, which encodes the GABA receptor alpha2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.

Entities: Chemical Disease Gene Mutation

Mesh：

Substances：

Year: 2010 PMID： 20202923 PMCID： PMC2841942 DOI： 10.1073/pnas.0911109107

Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205

42 in total

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270 in total

Review 1. Genetics of alcoholism.

Authors: Priya A Iyer-Eimerbrink; John I Nurnberger
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4. Severe intellectual disability and autistic features associated with microduplication 2q23.1.

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7. PKNOX2 is associated with formal thought disorder in schizophrenia: a meta-analysis of two genome-wide association studies.

Authors: Ke-Sheng Wang; Qunyuan Zhang; Xuefeng Liu; Longyang Wu; Min Zeng
Journal: J Mol Neurosci Date: 2012-05-31 Impact factor: 3.444

A genome-wide association study of alcohol dependence.

1. Implementing a unified approach to family-based tests of association.

Review 2. The Harvard Twin Study of Substance Abuse: what we have learned.

3. Statistical significance for genomewide studies.

Review 4. Actual causes of death in the United States, 2000.

5. Drinking problems in adopted and nonadopted sons of alcoholics.

6. Alcohol problems in adoptees raised apart from alcoholic biological parents.

7. Alcoholism susceptibility loci: confirmation studies in a replicate sample and further mapping.

8. Age at onset of alcohol use and DSM-IV alcohol abuse and dependence: a 12-year follow-up.

9. Allelic and haplotypic association of GABRA2 with alcohol dependence.

10. Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations.

Review 1. Genetics of alcoholism.

Review 2. Neuroimaging insights into the role of cortical GABA systems and the influence of nicotine on the recovery from alcohol dependence.

3. Genome-wide association study identifies 5q21 and 9p24.1 (KDM4C) loci associated with alcohol withdrawal symptoms.

4. Severe intellectual disability and autistic features associated with microduplication 2q23.1.

Review 5. Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges.

6. Genome-wide association study of alcohol dependence implicates KIAA0040 on chromosome 1q.

7. PKNOX2 is associated with formal thought disorder in schizophrenia: a meta-analysis of two genome-wide association studies.

8. Shared genetic factors influence risk for bipolar disorder and alcohol use disorders.

9. Genetic association test for multiple traits at gene level.

Review 10. GABA_A receptor polymorphisms in alcohol use disorder in the GWAS era.

Review 2. The Harvard Twin Study of Substance Abuse: what we have learned.

Review 4. Actual causes of death in the United States, 2000.

Review 1. Genetics of alcoholism.

Review 2. Neuroimaging insights into the role of cortical GABA systems and the influence of nicotine on the recovery from alcohol dependence.

Review 5. Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges.

Review 10. GABAA receptor polymorphisms in alcohol use disorder in the GWAS era.

Review 10. GABA_A receptor polymorphisms in alcohol use disorder in the GWAS era.