Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biochem Pharmacol. 2008 Jan 1;75(1):98-111. Epub 2007 Jul 25.

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

Author information

  • 1Molecular Neurobiology Branch, NIH-IRP (NIDA), Suite 3510, 333 Cassell Drive Baltimore, MD 21224, USA. guhl@intra.nida.nih.gov

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.

PMID:
17764662
[PubMed - indexed for MEDLINE]
PMCID:
PMC3282179
Free PMC Article

Images from this publication.See all images (1)Free text

Figure 1
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk