Association of alcohol craving with alpha-synuclein (SNCA).
BACKGROUND
Studies have found that genomic variation in the gene SNCA, which encodes the protein alpha-synuclein, may contribute to the variation in alcohol consumption in an inbred rat model of alcohol preference. Studies in humans have provided support for an association between SNCA and craving for alcohol.


METHODS
To examine the role of this gene in alcohol dependence and related phenotypes, 30 single nucleotide polymorphisms (SNPs) were genotyped across the SNCA gene in a sample of 219 multiplex alcoholic families of European American descent. Two phenotypes, alcohol dependence and alcohol craving, were analyzed using the pedigree disequilibrium test.


RESULTS
There was no evidence of association between any of the SNCA SNPs and alcohol dependence (p>or=0.13). In contrast, 8 SNPs provided evidence of association (p<0.05) with the phenotype of alcohol craving. Haplotype analysis further supported evidence of an association with alcohol craving; a haplotype encompassing SNPs in intron 4 through the region downstream of the gene was overtransmitted to cravers and a second haplotype was overtransmitted to noncravers.


CONCLUSIONS
These results suggest that variation in SNCA contributes to alcohol craving, a common, although not uniform, feature of alcohol dependence.
Foroud
Tatiana
T
Indiana University School of Medicine, Indianapolis, Indiana 46202-5251, USA. tforoud@iupui.edu
Wetherill
Leah Flury
LF
Liang
Tiebing
T
Dick
Danielle M
DM
Hesselbrock
Victor
V
Kramer
John
J
Nurnberger
John
J
Schuckit
Marc
M
Carr
Lucinda
L
Porjesz
Bernice
B
Xuei
Xiaoling
X
Edenberg
Howard J
HJ
D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D030541:Databases, Genetic; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051844:alpha-Synuclein / Q000235:genetics* / Q000502:physiology
D051844:alpha-Synuclein