Polysubstance abuse-vulnerability genes: genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms.
Strong genetic contributions to drug abuse vulnerability are well documented, but few chromosomal locations for human drug-abuse vulnerability alleles have been confirmed. We now identify chromosomal markers whose alleles distinguish drug abusers from control individuals in each of two samples, on the basis of pooled-sample microarray and association analyses. Reproducibly positive chromosomal regions defined by these markers in conjunction with previous results were especially unlikely to have been identified by chance. Positive markers identify the alcohol dehydrogenase (ADH) locus, flank the brain-derived neurotropic factor (BDNF) locus, and mark seven other regions previously linked to vulnerability to nicotine or alcohol abuse. These data support polygenic contributions of common allelic variants to polysubstance abuse vulnerability.
Uhl
G R
GR
Molecular Neurobiology Branch, National Institute of Drug Abuse, National Institutes of Health, Baltimore, MD, USA. guhl@intra.nida.nih.gov
Liu
Q R
QR
Walther
D
D
Hess
J
J
Naiman
D
D
D000328:Adult; D000349:Africa / Q000208:ethnology; D000426:Alcohol Dehydrogenase / Q000235:genetics; D019973:Alcohol-Related Disorders / Q000235:genetics; D000483:Alleles; D044383:Black People / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D005060:Europe / Q000208:ethnology; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D020412:Multifactorial Inheritance / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D021101:Radiation Hybrid Mapping; D012984:Software; D019966:Substance-Related Disorders / Q000201:enzymology / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
D019208:Brain-Derived Neurotrophic Factor; D005819:Genetic Markers; D009538:Nicotine; D000426:Alcohol Dehydrogenase