Pooled association genome scanning: validation and use to identify addiction vulnerability loci in two samples.
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 poly-substance 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.
Liu
Qing-Rong
QR
Molecular Neurobiology Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Box 5180, Baltimore, MD 21224, USA.
Drgon
Tomas
T
Walther
Donna
D
Johnson
Catherine
C
Poleskaya
Oxanna
O
Hess
Judith
J
Uhl
George R
GR
D000328:Adult; D000349:Africa / Q000208:ethnology; D001741:Black or African American / Q000235:genetics; D016022:Case-Control Studies; D005060:Europe / Q000208:ethnology; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D016678:Genome; D023281:Genomics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D019966:Substance-Related Disorders / Q000235:genetics*; D044465:White People / Q000235:genetics