Journal article
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 and behavior, Vol.18(6), pp.e12580-n/a
07/2019
DOI: 10.1111/gbb.12580
PMCID: PMC6726116
PMID: 31099175
Abstract
Genetic 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.
Details
- Title: Subtitle
- 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
- Creators
- Leah Wetherill - Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University, Indianapolis, IndianaDongbing Lai - Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University, Indianapolis, IndianaEmma C Johnson - Department of Psychiatry, Washington University School of Medicine, Washington University, Saint Louis, MissouriAndrey Anokhin - Department of Psychiatry, Washington University School of Medicine, Washington University, Saint Louis, MissouriLance Bauer - Department of Psychiatry, University of Connecticut School of Medicine, University of Connecticut, Farmington, ConnecticutKathleen K Bucholz - Department of Psychiatry, Washington University School of Medicine, Washington University, Saint Louis, MissouriDanielle M Dick - Department of Psychology & College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VirginiaAhmad R Hariri - Department of Psychology, Duke Institute for Brain Sciences, Duke University, Durham, North CarolinaVictor Hesselbrock - Department of Psychiatry, University of Connecticut School of Medicine, University of Connecticut, Farmington, ConnecticutChella Kamarajan - SUNY. Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, New YorkJohn Kramer - Department of Psychiatry, University of Iowa Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IowaSamuel Kuperman - Department of Psychiatry, University of Iowa Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IowaJacquelyn L Meyers - SUNY. Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, New YorkJohn I Nurnberger Jr - Department of Psychiatry, Indiana University School of Medicine, Indiana University, Indianapolis, IndianaMarc Schuckit - Department of Psychiatry, University of California San Diego, San Diego, CaliforniaDenise M Scott - Departments of Pediatrics and Human Genetics, Howard University, Washington, District of ColumbiaRobert E Taylor - Department of Pharmacology, Howard University, Washington, District of ColumbiaJay Tischfield - Department of Genetics, Rutgers University, Piscataway, New JerseyBernice Porjesz - SUNY. Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, New YorkAlison M Goate - Department of Neuroscience, Icahn School of Medicine at Mt. Sinai, New York, New YorkHoward J Edenberg - Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indiana University, Indianapolis, IndianaTatiana Foroud - Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University, Indianapolis, IndianaRyan Bogdan - Department of Psychological and Brain Sciences, Washington University in Saint Louis, Saint Louis, MissouriArpana Agrawal - Department of Psychiatry, Washington University School of Medicine, Washington University, Saint Louis, Missouri
- Resource Type
- Journal article
- Publication Details
- Genes, brain and behavior, Vol.18(6), pp.e12580-n/a
- DOI
- 10.1111/gbb.12580
- PMID
- 31099175
- PMCID
- PMC6726116
- NLM abbreviation
- Genes Brain Behav
- ISSN
- 1601-183X
- eISSN
- 1601-183X
- Publisher
- England
- Grant note
- S10 OD018164 / NIH HHS K02AA018755 / NIAAA NIH HHS R01 AG049789 / NIA NIH HHS R01 DA040716 / NIDA NIH HHS U01 MH109536 / NIMH NIH HHS U01 MH109532 / NIMH NIH HHS K01 DA037914 / NIDA NIH HHS S10 OD018522 / NIH HHS R21 DA038834 / NIDA NIH HHS K02 DA032573 / NIDA NIH HHS R01 HD083614 / NICHD NIH HHS K01DA037914 / NIDA NIH HHS R01 DA033369 / NIDA NIH HHS HHSN268201200008I / NHLBI NIH HHS DA038834 / NIH HHS K02DA32573 / NIDA NIH HHS K02 AA018755 / NIAAA NIH HHS DA040716 / NIH HHS MH109532 / NIMH NIH HHS HHSN268201200008C / NHLBI NIH HHS R01-DA031579 / NIH HHS U01 AG052564 / NIA NIH HHS R01-AG049789 / NIH HHS AG052564 / NIH HHS HD083614 / NIH HHS U10 AA008401 / NIAAA NIH HHS DA033369 / NIDA NIH HHS AG045231 / NIH HHS R01 AG045231 / NIA NIH HHS R01 DA031579 / NIDA NIH HHS R01 DA040411 / NIDA NIH HHS
- Language
- English
- Date published
- 07/2019
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics
- Record Identifier
- 9984003488902771
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