Genome-wide association study identifies genes that may contribute to risk for developing heroin addiction.
OBJECTIVE
We have used genome-wide association studies to identify variants that are associated with vulnerability to develop heroin addiction.


METHODS
DNA from 325 methadone stabilized, former severe heroin addicts and 250 control individuals were pooled by ethnicity (Caucasian and African-American) and analyzed using the Affymetrix GeneChip Mapping 100 K Set. Genome-wide association tests were conducted.


RESULTS
The strongest association with vulnerability to develop heroin addiction, with experiment-wise significance (P=0.035), was found in Caucasians with the variant rs10494334, a variant in an unannotated region of the genome (1q23.3). In African Americans, the variant most significantly associated with the heroin addiction vulnerability was rs950302, found in the cytosolic dual specificity phosphatase 27 gene DUSP27 (point-wise P=0.0079). Furthermore, analysis of the top 500 variants with the most significant associations (point-wise P< or =0.0036) in Caucasians showed that three of these variants are clustered in the regulating synaptic membrane exocytosis protein 2 gene RIMS2. Of the top 500 variants in African-Americans (point-wise P< or =0.0238), three variants are in the cardiomyopathy associated 3 gene CMYA3.


CONCLUSIONS
This study identifies new genes and variants that may increase an individual's vulnerability to develop heroin addiction.
Nielsen
David A
DA
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York 10065, USA.
Ji
Fei
F
Yuferov
Vadim
V
Ho
Ann
A
He
Chunsheng
C
Ott
Jurg
J
Kreek
Mary Jeanne
MJ
D016022:Case-Control Studies; D002874:Chromosome Mapping; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006556:Heroin Dependence / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008691:Methadone / Q000627:therapeutic use; D020411:Oligonucleotide Array Sequence Analysis; D010749:Phosphoprotein Phosphatases / Q000235:genetics
D010749:Phosphoprotein Phosphatases; C522887:STYXL2 protein, human; D008691:Methadone