@article{6e891e38da1e48d0b156cb708acef582,
title = "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",
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 (h2 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.",
keywords = "African-American, European-American, GWAS, alcohol dependence, drug dependence, fMRI, genetics, heritability, neural reward, ventral striatum",
author = "Leah Wetherill and Dongbing Lai and Johnson, {Emma C.} and Andrey Anokhin and Lance Bauer and Bucholz, {Kathleen K.} and Dick, {Danielle M.} and Hariri, {Ahmad R.} and Victor Hesselbrock and Chella Kamarajan and John Kramer and Samuel Kuperman and Meyers, {Jacquelyn L.} and Nurnberger, {John I.} and Marc Schuckit and Scott, {Denise M.} and Taylor, {Robert E.} and Jay Tischfield and Bernice Porjesz and Goate, {Alison M.} and Edenberg, {Howard J.} and Tatiana Foroud and Ryan Bogdan and Arpana Agrawal",
note = "Funding Information: The Duke Neurogenetics Study is supported by Duke University and the National Institutes of Health (NIDA DA033369). Funding Information: This research is also supported by K02DA32573 (AA), MH109532 & DA040411 (AA, ECJ). Funding Information: We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, P. Michael Conneally, Raymond Crowe and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Funding Information: Foundation for the National Institutes of Health, Grant/Award Numbers: AG045231, AG052564, DA038834, DA040716, HD083614, R01-AG049789, R01-DA031579; National Institute of Mental Health, Grant/ Award Number: MH109532; National Institute on Alcohol Abuse and Alcoholism, Grant/ Award Numbers: K02AA018755, U10AA008401; National Institute on Drug Abuse, Grant/Award Numbers: DA032573, DA033369, K01DA037914, K02DA32573 Funding Information: Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268201200008I. A.A. receives additional funding support from NIDA (DA032573). A.P.A. receives additional funding support from NIH (HD083614, DA040716, DA038834). R.B. receives additional funding support from NIH (AG052564, HD083614, AG045231). D.D. receives additional funding from K02AA018755. A.H. receives additional funding support from NIH (Grant Nos. R01-DA031579 and R01-AG049789). J.M. receives additional funding support from NIDA (K01DA037914). Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society",
year = "2019",
month = jul,
doi = "10.1111/gbb.12580",
language = "English",
volume = "18",
journal = "Genes, Brain and Behavior",
issn = "1601-1848",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "6",
}