Confirmation and generalization of an alcohol-dependence locus on chromosome 10q.
Several genome scans on alcohol dependence (AD) and AD-related traits have been published. In this article, we present the results of a genome-wide linkage scan on AD and several related traits in 322 European-American (EA) families, and results of additional analysis in 335 African-American (AA) families that were the subject of a previous report. All families were initially ascertained for cocaine and/or opioid dependence. Non-parametric linkage analysis in the EA sample revealed suggestive linkages on chromosomes 7 (LOD=2.1 at 82.8 cM, p=0.0009) and 10 (LOD=3.0 at 137.7 cM, p=0.0001). The chromosome 10 linkage peak is 20 cM distal from a genome-wide significant linkage peak we observed previously in the AA sample. Parametric linkage analysis on chromosome 10 (assuming a recessive model, 80% penetrance, disease allele frequency=0.3) resulted in LOD scores of 2.7 at 136.7 cM and 1.9 at 121.7 cM in the EA and AA samples, respectively, with a combined sample genome-wide significant LOD score of 4.1 at 131.7 cM. To reduce heterogeneity of the AD phenotype, we also assessed linkage of chromosome 10 markers with the presence of alcohol withdrawal symptoms, one of the seven components of the DSM-IV diagnosis of AD. Suggestive evidence for linkage was observed in both populations with only 5 cM separating the location of the peak LOD scores despite a loss of power due to a smaller number of families informative for this trait. Results of our study confirm a chromosome 10 risk locus for AD in two genetically distinct populations and suggest that this locus may correspond more precisely to a specific component of the disorder.
Department of Medicine (Genetics Program), Boston University School of Medicine, Boston, MA, USA.
Carolien I
CI
Panhuysen
Henry R
HR
Kranzler
Yi
Y
Yu
Roger D
RD
Weiss
Kathleen
K
Brady
James
J
Poling
Lindsay A
LA
Farrer
Joel
J
Gelernter
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D020268:Alcohol-Induced Disorders, Nervous System / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019683:Penetrance; D044465:White People / Q000235:genetics; D055815:Young Adult