Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis.
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.
Edenberg
Howard J
HJ
Indiana University School of Medicine, Indianapolis, USA. edenberg@iupui.edu
Xuei
Xiaoling
X
Chen
Hui-Ju
HJ
Tian
Huijun
H
Wetherill
Leah Flury
LF
Dick
Danielle M
DM
Almasy
Laura
L
Bierut
Laura
L
Bucholz
Kathleen K
KK
Goate
Alison
A
Hesselbrock
Victor
V
Kuperman
Samuel
S
Nurnberger
John
J
Porjesz
Bernice
B
Rice
John
J
Schuckit
Marc
M
Tischfield
Jay
J
Begleiter
Henri
H
Foroud
Tatiana
T
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000201:enzymology* / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide
D000426:Alcohol Dehydrogenase