TY - JOUR
T1 - Association of alcohol dehydrogenase genes with alcohol dependence
T2 - A comprehensive analysis
AU - Edenberg, Howard J.
AU - Xuei, Xiaoling
AU - Chen, Hui Ju
AU - Tian, Huijun
AU - Wetherill, Leah Flury
AU - Dick, Danielle M.
AU - Almasy, Laura
AU - Bierut, Laura
AU - Bucholz, Kathleen K.
AU - Goate, Alison
AU - Hesselbrock, Victor
AU - Kuperman, Samuel
AU - Nurnberger, John
AU - Porjesz, Bernice
AU - Rice, John
AU - Schuckit, Marc
AU - Tischfield, Jay
AU - Begleiter, Henri
AU - Foroud, Tatiana
N1 - Funding Information:
We thank Jinghua Zhao, Gayathri Rajan, Christopher Rush and Robert George for technical assistance with genotyping and data organization. Genotyping facilities were provided by the Center for Medical Genomics at Indiana University School of Medicine, supported in part by the Indiana 21st Century Research and Technology Fund and the Indiana Genomics Initiative (INGEN, supported in part by the Lilly Endowment, Inc.). The Collaborative Study on the Genetics of Alcoholism (COGA) (Principal Investigator: H. Begleiter; Co-Principal Investigators: L. Bierut, H. Edenberg, V. Hesselbrock, B. Porjesz) includes nine different centers where data collection, analysis and storage take place. The nine sites and Principal Investigators and Co-investigators are: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr, P.M. Conneally, T. Foroud); University of Iowa (S. Kuperman, R. Crowe); SUNY Downstate Medical Center (B. Porjesz, H. Begleiter); Washington University in St Louis (L. Bierut, A. Goate, J. Rice); University of California at San Diego (M. Schuckit); Howard University (R. Taylor); Rutgers University (J. Tischfield); Southwest Foundation (L. Almasy). Zhaoxia Ren serves as the NIAAA Staff Collaborator. This national collaborative study is supported by the NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). In memory of Theodore Reich, M.D., Co-Principal Investigator of COGA since its inception and one of the founders of modern psychiatric genetics, we acknowledge his immeasurable and fundamental scientific contributions to COGA and the field.
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33646127794&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddl073
DO - 10.1093/hmg/ddl073
M3 - Article
C2 - 16571603
AN - SCOPUS:33646127794
SN - 0964-6906
VL - 15
SP - 1539
EP - 1549
JO - Human molecular genetics
JF - Human molecular genetics
IS - 9
ER -