"Higher order" addiction molecular genetics: Convergent data from genome-wide association in humans and mice

George R. Uhl, Tomas Drgon, Catherine Johnson, Oluwatosin O. Fatusin, Qing Rong Liu, Carlo Contoreggi, Chuan Yun Li, Kari Buck, John Jr Crabbe

Research output: Contribution to journalArticle

106 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)98-111
Number of pages14
JournalBiochemical Pharmacology
Volume75
Issue number1
DOIs
StatePublished - Jan 1 2008

Fingerprint

Methamphetamine
Molecular Biology
Genes
Alcohols
Genome
Barbiturates
Quantitative Trait Loci
Genome-Wide Association Study
Nicotine
African Americans
Maintenance
Phenotype
DNA
Specifications
Genetics

Keywords

  • Association genome scanning
  • Microarray
  • Neuronal connections
  • Pooled
  • Substance dependence

ASJC Scopus subject areas

  • Pharmacology

Cite this

"Higher order" addiction molecular genetics : Convergent data from genome-wide association in humans and mice. / Uhl, George R.; Drgon, Tomas; Johnson, Catherine; Fatusin, Oluwatosin O.; Liu, Qing Rong; Contoreggi, Carlo; Li, Chuan Yun; Buck, Kari; Crabbe, John Jr.

In: Biochemical Pharmacology, Vol. 75, No. 1, 01.01.2008, p. 98-111.

Research output: Contribution to journalArticle

Uhl, George R. ; Drgon, Tomas ; Johnson, Catherine ; Fatusin, Oluwatosin O. ; Liu, Qing Rong ; Contoreggi, Carlo ; Li, Chuan Yun ; Buck, Kari ; Crabbe, John Jr. / "Higher order" addiction molecular genetics : Convergent data from genome-wide association in humans and mice. In: Biochemical Pharmacology. 2008 ; Vol. 75, No. 1. pp. 98-111.
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