Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.
As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P < 0.025) with several LR phenotypes in a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.
Joslyn
Geoff
G
Ernest Gallo Clinic and Research Center, Emeryville, CA 94608, USA.
Brush
Gerry
G
Robertson
Margaret
M
Smith
Tom L
TL
Kalmijn
Jelger
J
Schuckit
Marc
M
White
Raymond L
RL
D000437:Alcoholism / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15; D000431:Ethanol / Q000494:pharmacology*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D009419:Nerve Tissue Proteins / Q000235:genetics; D009538:Nicotine; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics; D035781:Siblings; D019966:Substance-Related Disorders / Q000235:genetics
D000431:Ethanol; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D009538:Nicotine; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human