Addiction genetics and pleiotropic effects of common haplotypes that make polygenic contributions to vulnerability to substance dependence.
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.
Uhl
George R
GR
Molecular Neurobiology Branch, NIH-IRP (NIDA), Baltimore, Maryland 21224, USA. guhl@intra.nida.nih.gov
Drgon
Tomas
T
Johnson
Catherine
C
Liu
Qing-Rong
QR
D002352:Carrier Proteins / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D005625:Frontal Lobe / Q000473:pathology; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D020412:Multifactorial Inheritance / Q000235:genetics*; D010554:Personality Disorders / Q000209:etiology / Q000235:genetics; D010641:Phenotype; D019966:Substance-Related Disorders / Q000150:complications / Q000235:genetics* / Q000473:pathology
D002352:Carrier Proteins; D016207:Cytokines; C066845:pleiotrophin