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Human Molecular Genetics Advance Access originally published online on March 28, 2006
Human Molecular Genetics 2006 15(9):1539-1549; doi:10.1093/hmg/ddl073
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© The Author 2006. Published by Oxford University Press. All rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact: journals.permissions@oxfordjournals.org

Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis

Howard J. Edenberg1,*, Xiaoling Xuei1, Hui-Ju Chen1, Huijun Tian1, Leah Flury Wetherill1, Danielle M. Dick2, Laura Almasy3, Laura Bierut2, Kathleen K. Bucholz2, Alison Goate2, Victor Hesselbrock4, Samuel Kuperman5, John Nurnberger1, Bernice Porjesz6, John Rice2, Marc Schuckit7, Jay Tischfield8, Henri Begleiter6 and Tatiana Foroud1

1Indiana University School of Medicine, Indianapolis, IN, USA, 2Washington University School of Medicine, St Louis, MO, USA, 3Southwest Foundation for Biomedical Research, San Antonio, TX, USA, 4University of Connecticut, Farmington, CT, USA, 5University of Iowa Carver College of Medicine, Iowa City, IA, USA, 6SUNY Health Sciences Center, Brooklyn, NY, USA, 7University of California, San Diego, CA, USA and 8Rutgers University, Piscataway, NJ, USA

* To whom correspondence should be addressed. Tel: +1 3172742353; Fax: +1 3172744686; Email: edenberg{at}iupui.edu

Received January 18, 2006; Accepted March 22, 2006

Linkage evidence indicated that gene(s) located on chromosome 4q, in the region of the alcohol dehydrogenase (ADH) genes, affected risk for alcoholism. We genotyped 110 single nucleotide polymorphisms (SNPs) across the seven ADH genes and analyzed their association with alcoholism in a set of families with multiple alcoholic members, using the pedigree disequilibrium test. There was strong evidence that variations in ADH4 are associated with alcoholism: 12 SNPs were significantly associated. The region of strongest association ran from intron 1 to 19.5 kb beyond the 3' end of the gene. Haplotype tag SNPs were selected for the block in the ADH4 gene that provided evidence of association and subsequently used in association analysis; the haplotype was significantly associated with alcoholism (P=0.01) There was weaker evidence that variations in ADH1A and ADH1B might also play a role in modifying risk. Among African-Americans, there was evidence that the ADH1B*3 allele was protective.


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