Genome-wide association study identifies genes that may contribute to risk for developing heroin addiction

Objectives 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 100K 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 <= 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 <= 0.0238), three variants are in the cardiomyopathy associated 3 gene CMYA3. Conclusion This study identifies new genes and variants that may increase an individual's vulnerability to develop heroin addiction. Psychiatr Genet 20:207-214 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.