@article{8fdfdada5ea24461994d9536b546ad7a,
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.",
keywords = "Ancestry, Genetic association study, Haplotype, Heroin, Opioid, Replication, Rs1344706, Rs7597593, Urban Health Study, ZNF804A",
author = "Hancock, {D. B.} and Levy, {J. L.} and Gaddis, {N. C.} and C. Glasheen and Saccone, {N. L.} and Page, {G. P.} and Bierut, {L. J.} and Kral, {A. H.} and Johnson, {E. O.}",
note = "Funding Information: This study was supported by the National Institute of Drug Abuse grant numbers R33 DA027486 and R01 DA026141. Heroin addiction cases were drawn from the Urban Health Study (UHS) and genotyped at the Center for Inherited Disease Research at Johns Hopkins University. Their data are deposited at dbGaP (phs000454.v1.p1). Controls for comparison to the UHS heroin addiction cases were drawn from the following six cohorts in dbGaP: 1 Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI) (U01 HG004422). SAGE is one of the genome-wide association studies (GWAS) funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the NCBI. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392) and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR), was provided by the NIH GEI (U01 HG004438), the National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse and the NIH contract ''High throughput genotyping for studying the genetic contributions to human disease'' (HHSN268200782096C). The datasets used for the analyses described in this manuscript were obtained via dbGaP accession number phs000092.v1.p1. The authors acknowledge the contribution of data from ''Genetic Architecture of Smoking and Smoking Cessation'' accessed through dbGaP accession number phs000404.v1.p1. Funding support for genotyping, which was performed at CIDR, was provided by X01 HG005274. CIDR is fully funded through a federal contract from the NIH to The Johns Hopkins University, contract number HHSN268200782096C. Assistance with genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Funding support for collection of datasets and samples was provided by COGEND (P01 CA089392) and the University of Wisconsin Transdisciplinary Tobacco Use Research Center (P50 DA019706 and P50 CA084724). Funding support for the GWAS of Ischemic Stroke study was provided through the NIH GEI (U01 HG004436). The GWAS of Ischemic Stroke study is one of the GWAS funded as part of GENEVA under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the NCBI. Funding support for genotyping, which was performed at The Johns Hopkins University CIDR, was provided by the NIH GEI (U01 HG004438) and NIH contract number HHSN268200782096C. Field work for this project was supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention; the National Institute of Neurological Disorders and Stroke (NINDS) and the NIH Office of Research on Women''s Health (ORWH) (R01 NS045012); Office of Research and Development, Medical Research Service, Department of Veterans Affairs and the University of Maryland General Clinical Research Center (M01 RR165001), National Center for Research Resources, NIH. This study used samples from the NINDS Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds). The datasets used for the analyses described in this manuscript were obtained via dbGaP accession number phs000292.v1.p1. Funding support for the GENEVA Prostate Cancer study was provided through the National Cancer Institute (R37 CA054281, R01 CA063464, P01 CA033619, U01 CA0136792, U01 CA098758 and RC2 CA148085) and the Nationaumanl Genome Research Institute (U01 HG004726). Assistance with phenotype harmonization, SNP selection, data cleaning, meta-analyses, data management and dissemination and general study coordination was provided by the GENEVA Coordinating Center (U01 HG004789). The datasets used for the analyses described in this manuscript were obtained from dbGaP at phs000306.v2.p1. This work utilized in part data from the NINDS dbGaP database from the CIDR NeuroGenetics Research Consortium (NGRC) Parkinson''s disease study (accession number phs000196.v2.p1). For the ''High Density SNP Association Analysis of Melanoma: Case-control and Outcomes Investigation'', research support to collect data and develop an application to support this project was provided by P50 CA093459, P50 CA097007, R01 ES011740 and R01 CA133996 (dbGaP accession number phs000187.v1.p1). L.B.J. and the spouse of N.L.S. are listed as inventors on Issued U.S. Patent 8080371, ''Markers for Addiction'', covering the use of certain SNPs in determining the diagnosis, prognosis and treatment of addiction. Otherwise, the authors have no conflicts of interest. Publisher Copyright: {\textcopyright} 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.",
year = "2015",
month = nov,
day = "1",
doi = "10.1111/gbb.12254",
language = "English",
volume = "14",
pages = "635--640",
journal = "Genes, Brain and Behavior",
issn = "1601-1848",
number = "8",
}