Replication of ZNF804A gene variant associations with risk of heroin addiction
Year: 2015
Type: article
Study design: Observational Study
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.
Source: Genes Brain & Behavior
DOI: 10.1111/gbb.12254
Institutions: RTI International, Washington University in St. Louis
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Johns Hopkins University, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences
Awards: G1083756078, G132635143, G1621215609, G2265115783, G2313542652, G2548880556, Study of Addiction: Genetics and Environment, M D Anderson Cancer Center Head & Neck SPORE, G2851966638, Molecular Epidemiology of DNA Repair in Head and Neck Cancer, G3276551827, G3457954119, G3799582765, Genome Wide Association Coordinating Center, G4808091200, JH/CIDR Genotyping for Genome-Wide Association Studies, Genetic Risk to Stroke in Smokers and Nonsmokers in Two Ethnic Groups, FAMILY STUDY OF COCAINE DEPENDENCE, G693077865, G721666067, Molecular Epidemiology of Nutrition and Cancer in the Multiethnic Cohort Study, G8267674335, G8330773770, G858805679, Genetics of Early Onset-Stroke, G948540326, The University of Texas M. D. Anderson Cancer Center SPORE in Melanoma
OpenAlex ID: W2132482206