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. 2010 May;35(6):1325-32.
doi: 10.1038/npp.2010.1. Epub 2010 Feb 10.

Confirmation and generalization of an alcohol-dependence locus on chromosome 10q

Carolien I Panhuysen  1 , Henry R Kranzler, Yi Yu, Roger D Weiss, Kathleen Brady, James Poling, Lindsay A Farrer, Joel Gelernter
Affiliations

Confirmation and generalization of an alcohol-dependence locus on chromosome 10q

Carolien I Panhuysen et al. Neuropsychopharmacology. 2010 May.

Abstract

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.

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Figures

Figure 1
Figure 1
Non-parametric genome-wide linkage scan of DSM-IV diagnosis of AD in 95 EA families.
Figure 2
Figure 2
Cumulative parametric LOD scores of AD on chromosome 10 in EA and AA populations assuming a recessive model. (see Methods section for details). Only LOD scores greater than zero are shown.
Figure 3
Figure 3
Cumulative percentage of subjects reporting the seven separate SSADDA items related to AD. Subjects reporting three or more items are assigned a DSM-IV diagnosis of AD. The dotted line represents the number of subjects reporting an increase in alcohol tolerance. The dashed line represents the number of subjects reporting withdrawal symptoms.
Figure 4
Figure 4
Non-parametric linkage results of AD and alcohol withdrawal symptoms with markers on chromosome 10 in EA and AA families.
See this image and copyright information in PMC

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