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dc.contributor.authorWetherill, Leah
dc.contributor.authorLai, Dongbing
dc.contributor.authorJohnson, Emma C
dc.contributor.authorAnokhin, Andrey
dc.contributor.authorBauer, Lance
dc.contributor.authorBucholz, Kathleen K
dc.contributor.authorDick, Danielle M
dc.contributor.authorHariri, Ahmad R
dc.contributor.authorHesselbrock, Victor
dc.contributor.authorKamarajan, Chella
dc.contributor.authorKramer, John
dc.contributor.authorKuperman, Samuel
dc.contributor.authorMeyers, Jacquelyn L
dc.contributor.authorNurnberger, John I
dc.contributor.authorSchuckit, Marc
dc.contributor.authorScott, Denise M
dc.contributor.authorTaylor, Robert E
dc.contributor.authorTischfield, Jay
dc.contributor.authorPorjesz, Bernice
dc.contributor.authorGoate, Alison M
dc.contributor.authorEdenberg, Howard J
dc.contributor.authorForoud, Tatiana
dc.contributor.authorBogdan, Ryan
dc.contributor.authorAgrawal, Arpana
dc.date.accessioned2022-12-09T17:35:20Z
dc.date.available2022-12-09T17:35:20Z
dc.date.issued2019-06-11
dc.identifier.citationWetherill L, Lai D, Johnson EC, Anokhin A, Bauer L, Bucholz KK, Dick DM, Hariri AR, Hesselbrock V, Kamarajan C, Kramer J, Kuperman S, Meyers JL, Nurnberger JI Jr, Schuckit M, Scott DM, Taylor RE, Tischfield J, Porjesz B, Goate AM, Edenberg HJ, Foroud T, Bogdan R, Agrawal A. Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans. Genes Brain Behav. 2019 Jul;18(6):e12580. doi: 10.1111/gbb.12580. Epub 2019 Jun 11. Erratum in: Genes Brain Behav. 2019 Nov;18(8):e12608. PMID: 31099175; PMCID: PMC6726116.en_US
dc.identifier.eissn1601-183X
dc.identifier.doi10.1111/gbb.12580
dc.identifier.pmid31099175
dc.identifier.urihttp://hdl.handle.net/20.500.12648/7937
dc.description.abstractGenetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk.en_US
dc.language.isoenen_US
dc.relation.urlhttps://onlinelibrary.wiley.com/doi/10.1111/gbb.12580en_US
dc.rights© 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAfrican-Americanen_US
dc.subjectEuropean-Americanen_US
dc.subjectGWASen_US
dc.subjectalcohol dependenceen_US
dc.subjectdrug dependenceen_US
dc.subjectfMRIen_US
dc.subjectgeneticsen_US
dc.subjectheritabilityen_US
dc.subjectneural rewarden_US
dc.subjectventral striatumen_US
dc.titleGenome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.en_US
dc.typeArticle/Reviewen_US
dc.source.journaltitleGenes, brain, and behavioren_US
dc.source.volume18
dc.source.issue6
dc.source.beginpagee12580
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.description.versionVoRen_US
refterms.dateFOA2022-12-09T17:35:20Z
dc.description.institutionSUNY Downstateen_US
dc.description.departmentHenri Begleiter Neurodynamics Laboratoryen_US
dc.description.degreelevelN/Aen_US
dc.identifier.journalGenes, brain, and behavior


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© 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
Except where otherwise noted, this item's license is described as © 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.