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Chunk #51 — 5. GWAS for drug addiction/dependence

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Implications of genome wide association studies for addiction: are our a priori assumptions all wrong?
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Beginning in the late 1990s the MNB at NIDA began a series of GWAS examining drug dependence. The first GWAS to examine drug (polysubstance) dependence, and one of the first studies to take this approach in any complex disorder, used less than 1500 single nucleotide polymorphisms (SNPs) in European-American and African-American drug dependent subjects (G. R. Uhl, Liu, Walther, Hess, & Naiman, 2001). This marker density was obviously not sufficient to identify many individual genes, so the authors spoke of “chromosomal” regions. Nonetheless, this analysis identified a number of regions consistent with previous linkage-based genome scans (Foroud, et al., 2000; Long, et al., 1998; Reich, et al., 1998; Straub, et al., 1999) and a number of loci that were not identified in previous studies. Part of the strategy used in this, and many subsequent MNB studies, was to do comparisons in both European-American and African-American subjects and to look for replication in terms of identification of the same chromosomal regions between these independent samples (Drgon, et al., 2011; Q. R. Liu, et al., 2006; G. R. Uhl, Liu, & Walther,