title: Replication of ZNF804A gene variant associations with risk of heroin addiction.
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.
authors.affiliation: Behavioral and Urban Health Program, Behavioral Health and Criminal Justice Division, NC, USA.
authors.forename: D B
authors.identifier: http://orcid.org/0000-0003-2240-3604
authors.initials: DB
authors.lastname: Hancock
authors.affiliation: Research Computing Division, RTI International, Research Triangle Park, NC, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Levy
authors.affiliation: Research Computing Division, RTI International, Research Triangle Park, NC, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Gaddis
authors.affiliation: Behavioral and Urban Health Program, Behavioral Health and Criminal Justice Division, NC, USA.
authors.forename: C
authors.initials: C
authors.lastname: Glasheen
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Saccone
authors.affiliation: Fellow Program, Center for Genomics in Public Health and Medicine, RTI International, Atlanta, GA, USA.
authors.forename: G P
authors.initials: GP
authors.lastname: Page
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Bierut
authors.affiliation: Behavioral and Urban Health Program, Behavioral Health and Criminal Justice Division, RTI International, San Francisco, CA, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Kral
authors.affiliation: Fellow Program and Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC, USA.
authors.forename: E O
authors.initials: EO
authors.lastname: Johnson
mesh_terms: D000483:Alleles; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006556:Heroin Dependence / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human
keywords: Ancestry; Urban Health Study; ZNF804A; genetic association study; haplotype; heroin; opioid; replication; rs1344706; rs7597593