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Chunk #3 — Introduction

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Genome-Wide Association of Heroin Dependence in Han Chinese.
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Genome wide association studies (GWAS) testing heroin addiction [11,12] and opioid dependence [13,14] have produced evidence of the role of novel loci and even replicated evidence from candidate gene studies. In the very first GWAS on heroin addiction, [11], testing 104 methadone-maintained former heroin addicts of Caucasian ethnicity and 101 matched controls, the authors reported suggestive association with GABRA3 (gamma-aminobutyric acid, receptor subunit alpha 3), a candidate gene for heroin addiction. Despite the small sample size, one marker (rs965972; chr1q31.2) survived correction for multiple testing, however it was not located near any gene. Building on these early findings, the authors expanded the study by increasing the sample size as well as the number of markers tested [12]; 325 ethnically mixed, methadone-stabilized former heroin addicts were compared to 250 control individuals using a 100K Affymetrix array. Some overlap was observed between the two studies, whereby the top markers were located on chromosome 1q23, albeit about 30kb apart. In the African-American sub-sample (125 cases; 100 controls), the most significant SNP (rs950302) was located in the gene DUSP27 (cytosolic dual specificity phosphatase 27), with point-wise significance (p = 0.0079) for association with heroin addiction vulnerability.