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

Abstract

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 subjects 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 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. Conclusions This study identifies new genes and variants that may increase an individual’s vulnerability to develop heroin addiction.

An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans

“…Differences in the response to exogenous opioids between ancestral populations have previously been observed (Bayerer et al, 2007;Nielsen et al, 2010). The effect of butorphanol and morphine on certain types of analgesia is greater in African-Americans compared with nonHispanic whites (Sibille et al, 2011).…”

Identification of SSR markers associated with height using pool-based genome-wide association mapping in sorghum

“…But this method identified one strong association in Caucasians with rs10494334, a marker in an unannotated region of the human genome. In African Americans, the marker most significantly associated with the heroin addiction vulnerability was found in the cytosolic dual specificity phosphatase 27 gene DUSP27 (Nielsen et al 2010). These results indicate that markers associated with quantitative traits can be identified in genomewide screening using the pool-based association mapping and these markers can be a powerful tool in identifying these genes and in markerassisted breeding to genetically improve sorghum as a bioenergy crop.…”

Genome-Wide Association Studies of Alcohol Dependence and Substance Use Disorders

“…Nielsen et al [36] conducted a pooled GWAS (100K chip) in a comparatively small sample consisting of 325 former heroin addicts (200 Caucasian, 125 African American) and 250 controls (150 Caucasian, 100 African American). The strongest association was detected in Caucasians for the variant rs10494334, which is located at chr1q23.…”