| Title | "Higher order" addiction molecular genetics: Convergent data from genome-wide association in humans and mice |
| Authors | Uhl, George R. Drgon, Tomas Johnson, Catherine Fatusin, Olutuatosin O. Liu, Qing-Rong Contoreggi, Carlo Li, Chuan-Yun Buck, Kari Crabbe, John |
| Affiliation | NIDA, Mol Neurobiol Branch, NIH, IRP, Baltimore, MD 21224 USA. NIDA, Off Clin Director, NIH, IRP, Baltimore, MD 21224 USA. Peking Univ, Coll Life Sci, Ctr Bioinformat, Beijing 100871, Peoples R China. Oregon Hlth & Sci Univ, Potland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Box 5180, Baltimore, MD 21224 USA. |
| Keywords | association genome scanning substance dependence microarray pooled neuronal connections ALDEHYDE DEHYDROGENASE GENOTYPES ALCOHOL-METABOLIZING GENES CELL-ADHESION MOLECULES POPULATION-BASED SAMPLE MILD MENTAL IMPAIRMENT INBRED MOUSE STRAINS NICOTINE DEPENDENCE SUSCEPTIBILITY LOCI LINKAGE ANALYSIS SUBSTANCE-ABUSE |
| Issue Date | 2008 |
| Publisher | biochemical pharmacology |
| Citation | BIOCHEMICAL PHARMACOLOGY.2008,75,(1),98-111. |
| Abstract | 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. Published by Elsevier Inc. |
| URI | http://hdl.handle.net/20.500.11897/249083 |
| ISSN | 0006-2952 |
| DOI | 10.1016/j.bcp.2007.06.042 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 |
