"Higher order" addiction molecular genetics: convergent data from genome-wide association in humans and mice.
paper
Cited
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- Authors
- Uhl, George R; Drgon, Tomas; Johnson, Catherine; Fatusin, Oluwatosin O; Liu, Qing-Rong; Contoreggi, Carlo; Li, Chuan-Yun; Buck, Kari; Crabbe, John
- Year
- 2008
- Journal
- Biochemical pharmacology
- PMID
- 17764662
- DOI
- 10.1016/j.bcp.2007.06.042
- PMCID
- PMC3282179
Family, adoption and twin data each support substantial heritability for addictions. Most of this heritable influence is not substance-specific. The overlapping genetic vulnerability for developing dependence on a variety of addictive substances suggests large roles for "higher order" pharamacogenomics in addiction molecular genetics. We and others have now completed genome-wide association (GWA) studies of DNAs from individuals with dependence on a variety of addictive substances versus appropriate controls. Recently reported replicated GWA observations identify a number of genes based on comparisons between controls and European-American and African-American polysubstance abusers. Here we review the convergence between these results and data that compares control samples and (a) alcohol-dependent European-Americans, (b) methamphetamine-dependent Asians and (c) nicotine dependent samples from European backgrounds. We also compare these human data to quantitative trait locus (QTL) results from studies of addiction-related phenotypes in mice that focus on alcohol, methamphetamine and barbiturates. These comparisons support a genetic architecture built from largely polygenic contributions of common allelic variants to dependence on a variety of legal and illegal substances. Many of the gene variants identified in this way are likely to alter specification and maintenance of neuronal connections.
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