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Genes Brain Behav. 2015 Nov;14(8):635-40. doi: 10.1111/gbb.12254. Epub 2015 Oct 20.

Replication of ZNF804A gene variant associations with risk of heroin addiction.

Author information

1
Behavioral and Urban Health Program, Behavioral Health and Criminal Justice Division, NC, USA.
2
Research Computing Division, RTI International, Research Triangle Park, NC, USA.
3
Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
4
Fellow Program, Center for Genomics in Public Health and Medicine, RTI International, Atlanta, GA, USA.
5
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
6
Behavioral and Urban Health Program, Behavioral Health and Criminal Justice Division, RTI International, San Francisco, CA, USA.
7
Fellow Program and Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC, USA.

Abstract

Heroin addiction is heritable, but few specific genetic variants have been reproducibly associated with this disease. The zinc finger protein 804A (ZNF804A) gene is a biologically plausible susceptibility gene for heroin addiction, given its function as a transcription factor in human brain. Novel associations of two common ZNF804A single nucleotide polymorphisms (SNPs), rs7597593 and rs1344706, with heroin addiction have been reported in Han Chinese. Both SNPs have also been implicated for regulating ZNF804A expression in human brain, including the addiction-relevant dorsolateral prefrontal cortex. In this independent replication study, we tested the rs7597593 and rs1344706 SNP genotypes and their corresponding haplotypes for association with heroin addiction using cases drawn from the Urban Health Study and population controls: total N = 10 757 [7095 European Americans (EAs) and 3662 African Americans (AAs)]. We independently replicated both ZNF804A SNP associations in EAs: the rs7597593-T (P = 0.016) and rs1344706-A (P = 0.029) alleles both being associated with increased risk of heroin addiction, consistent with the prior report. Neither SNP was associated in AAs alone, but meta-analysis across both ancestry groups resulted in significant associations for rs1344706-A [P = 0.016, odds ratio (95% confidence interval) = 1.13 (1.02-1.25)] and its haplotype with rs7597593-T [P = 0.0067, odds ratio (95% confidence interval) = 1.16 (1.04-1.29)]. By showing consistent associations across independent studies and diverse ancestry groups, our study provides evidence that these two ZNF804A SNPs and their risk haplotype are among the few replicable genetic associations with heroin addiction.

KEYWORDS:

Ancestry; Urban Health Study; ZNF804A; genetic association study; haplotype; heroin; opioid; replication; rs1344706; rs7597593

PMID:
26382569
PMCID:
PMC4715582
DOI:
10.1111/gbb.12254
[Indexed for MEDLINE]
Free PMC Article

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