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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Acknowledgements
We thank John Farrell and Michael Jervis for database management support. This work was supported by NIDA grants R01 DA12690, R01 DA12849, R01 AA11330, K24 DA15105, and K24 DA022288 and NIAAA grant K24 AA013736. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University contract number N01-HG-65403.
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Dr Kranzler has received consulting fees from Ortho-McNeil Pharmaceuticals, H. Lundbeck A/S, Forest Pharmaceuticals, elbion NV, Sanofi-Aventis, Solvay Pharmaceuticals, and Alkermes, Inc. He has received research support from Ortho-McNeil Pharmaceuticals, Bristol-Myers Squibb Company, and Merck & Co., Inc. and honoraria from Forest Pharmaceuticals, Alkermes, Inc., and the American College of Neuropsychopharmacology. Dr Farrer has received consulting fees from Novartis Pharmaceuticals and research support from Eisai Pharmaceuticals. Dr Gelernter reports that he has received compensation for professional services in the previous 3 years from the following entities: Yale University School of Medicine, Veterans Affairs Healthcare System (VA) and the National Institutes of Health (NIAAA, NIDA, and NIMH) and related to academic lectures and editorial functions in various scientific venues (including the ACNP). None of the other authors has anything to disclose.
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Panhuysen, C., Kranzler, H., Yu, Y. et al. Confirmation and Generalization of an Alcohol-Dependence Locus on Chromosome 10q. Neuropsychopharmacol 35, 1325–1332 (2010). https://doi.org/10.1038/npp.2010.1
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DOI: https://doi.org/10.1038/npp.2010.1
