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Pooled Association Genome Scanning: Validation and Use to Identify Addiction Vulnerability Loci in Two Samples
Qing-Rong Liu, Tomas Drgon, Donna Walther, Catherine Johnson, Oxanna Poleskaya, Judith Hess, George R. Uhl and Raymond L. White
Proceedings of the National Academy of Sciences of the United States of America
Vol. 102, No. 33 (Aug. 16, 2005), pp. 11864-11869
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3376361
Page Count: 6
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Association genome scanning is of increasing interest for identifying the chromosomal regions that contain gene variants that contribute to vulnerability to complex disorders, including addictions. To improve the power and feasibility of this approach, we have validated "10k" microarray-based allelic frequency assessments in pooled DNA samples and have used this approach to seek allelic frequency differences between heavy polysubstance abusers and well characterized control individuals. Thirty-eight loci contain SNPs that display robust allele frequency differences between abusers and controls in both European- and African-American samples. These loci identify an alcohol/acetaldehyde dehydrogenase gene cluster and genes implicated in cellular signaling, gene regulation, development, "cell adhesion," and Mendelian disorders. The results converge with previous linkage and association results for addictions. Pooled association genome scanning provides a useful tool for elucidating molecular genetic underpinnings of complex disorders and identifies both previously understood and previously unanticipated mechanisms for addiction vulnerability.
Proceedings of the National Academy of Sciences of the United States of America © 2005 National Academy of Sciences