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 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≤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.
aLaboratory of the Biology of Addictive Diseases
bLaboratory of Statistical Genetics, The Rockefeller University, New York
cMenninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, and Michael E. DeBakey V.A. Medical Center, Houston, Texas, Houston, USA
dBeijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
Correspondence to Professor Mary Jeanne Kreek, MD, Laboratory of the Biology of Addictive Diseases, The Rockefeller University, Box 171, 1230 York Avenue, NY 10065, USA
Tel: +212 327 8490; fax: +212 327 8574;
Received 28 January 2009 Revised 29 October 2009 Accepted 1 January 2010
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