Addiction genetics and pleiotropic effects of common haplotypes that make polygenic contributions to vulnerability to substance dependence

George R. Uhl, Tomas Drgon, Catherine Johnson, Qing Rong Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Abundant evidence from family, adoption, and twin studies point to large genetic contributions to individual differences in vulnerability to develop dependence on one or more addictive substances. Twin data suggest that most of this genetic vulnerability is shared by individuals who are dependent on a variety of addictive substances. Molecular genetic studies, especially genomewide and candidate gene association studies, have elucidated common haplotypes in dozens of genes that appear to make polygenic contributions to vulnerability to developing dependence. Most genes that harbor currently identified addiction-associated haplotypes are expressed in the brain. Haplotypes in many of the same genes are identified in genomewide association studies that compare allele frequencies in substance dependent vs. control individuals from European, African, and Asian racial/ethnic backgrounds. Many of these addiction-associated haplotypes display pleiotropic influences on a variety of related brain-based phenotypes that display 1) substantial heritability and 2) clinical cooccurence with substance dependence.

Original languageEnglish (US)
Pages (from-to)272-282
Number of pages11
JournalJournal of Neurogenetics
Volume23
Issue number3
DOIs
StatePublished - Jan 2009
Externally publishedYes

Keywords

  • Addiction
  • Complex genetics
  • Genomewide association
  • Psychiatric genetics

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Genetics

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