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

Howard J. Edenberg, Xiaoling Xuei, Hui Ju Chen, Huijun Tian, Leah Flury Wetherill, Danielle M. Dick, Laura Almasy, Laura Bierut, Kathleen K. Bucholz, Alison Goate, Victor Hesselbrock, Samuel Kuperman, John Nurnberger, Bernice Porjesz, John Rice, Marc Schuckit, Jay Tischfield, Henri Begleiter, Tatiana Foroud

Research output: Contribution to journalArticle

185 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1539-1549
Number of pages11
JournalHuman molecular genetics
Volume15
Issue number9
DOIs
StatePublished - May 1 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Edenberg, H. J., Xuei, X., Chen, H. J., Tian, H., Wetherill, L. F., Dick, D. M., Almasy, L., Bierut, L., Bucholz, K. K., Goate, A., Hesselbrock, V., Kuperman, S., Nurnberger, J., Porjesz, B., Rice, J., Schuckit, M., Tischfield, J., Begleiter, H., & Foroud, T. (2006). Association of alcohol dehydrogenase genes with alcohol dependence: A comprehensive analysis. Human molecular genetics, 15(9), 1539-1549. https://doi.org/10.1093/hmg/ddl073