BACKGROUND: Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk. METHODS: We carried out a genome-wide association study (GWAS) on a case-control sample drawn from the families in the Collaborative Study on the Genetics of Alcoholism. The cases all met diagnostic criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition; controls all consumed alcohol but were not dependent on alcohol or illicit drugs. To prioritize among the strongest candidates, we genotyped most of the top 199 single nucleotide polymorphisms (SNPs) (p < or = 2.1 x 10(-4)) in a sample of alcohol-dependent families and performed pedigree-based association analysis. We also examined whether the genes harboring the top SNPs were expressed in human brain or were differentially expressed in the presence of ethanol in lymphoblastoid cells. RESULTS: Although no single SNP met genome-wide criteria for significance, there were several clusters of SNPs that provided mutual support. Combining evidence from the case-control study, the follow-up in families, and gene expression provided strongest support for the association of a cluster of genes on chromosome 11 (SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5) with alcohol dependence. Several SNPs nominated as candidates in earlier GWAS studies replicated in ours, including CPE, DNASE2B, SLC10A2, ARL6IP5, ID4, GATA4, SYNE1, and ADCY3. CONCLUSIONS: We have identified several promising associations that warrant further examination in independent samples.
BACKGROUND:Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk. METHODS: We carried out a genome-wide association study (GWAS) on a case-control sample drawn from the families in the Collaborative Study on the Genetics of Alcoholism. The cases all met diagnostic criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition; controls all consumed alcohol but were not dependent on alcohol or illicit drugs. To prioritize among the strongest candidates, we genotyped most of the top 199 single nucleotide polymorphisms (SNPs) (p < or = 2.1 x 10(-4)) in a sample of alcohol-dependent families and performed pedigree-based association analysis. We also examined whether the genes harboring the top SNPs were expressed in human brain or were differentially expressed in the presence of ethanol in lymphoblastoid cells. RESULTS: Although no single SNP met genome-wide criteria for significance, there were several clusters of SNPs that provided mutual support. Combining evidence from the case-control study, the follow-up in families, and gene expression provided strongest support for the association of a cluster of genes on chromosome 11 (SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5) with alcohol dependence. Several SNPs nominated as candidates in earlier GWAS studies replicated in ours, including CPE, DNASE2B, SLC10A2, ARL6IP5, ID4, GATA4, SYNE1, and ADCY3. CONCLUSIONS: We have identified several promising associations that warrant further examination in independent samples.
Authors: Arpana Agrawal; Howard J Edenberg; Tatiana Foroud; Laura J Bierut; Gerald Dunne; Anthony L Hinrichs; John I Nurnberger; Raymond Crowe; Samuel Kuperman; Marc A Schuckit; Henri Begleiter; Bernice Porjesz; Danielle M Dick Journal: Behav Genet Date: 2006-09 Impact factor: 2.805
Authors: Andrew D Johnson; Robert E Handsaker; Sara L Pulit; Marcia M Nizzari; Christopher J O'Donnell; Paul I W de Bakker Journal: Bioinformatics Date: 2008-10-30 Impact factor: 6.937
Authors: Jaakko Lappalainen; Evgeny Krupitsky; Mikhail Remizov; Sofia Pchelina; Anastaisa Taraskina; Edwin Zvartau; Lucia K Somberg; Jonathan Covault; Henry R Kranzler; John H Krystal; Joel Gelernter Journal: Alcohol Clin Exp Res Date: 2005-04 Impact factor: 3.455
Authors: Joseph T Sakai; Thomas J Crowley; Michael C Stallings; Matthew McQueen; John K Hewitt; Christian Hopfer; Nicole R Hoft; Marissa A Ehringer Journal: Psychiatr Genet Date: 2012-04 Impact factor: 2.458
Authors: Brion S Maher; Vladimir I Vladimirov; Shawn J Latendresse; Dawn L Thiselton; Rebecca McNamee; Moonsu Kang; Tim B Bigdeli; Xiangning Chen; Brien P Riley; John M Hettema; Howard Chilcoat; Christian Heidbreder; Pierandrea Muglia; E Lenn Murrelle; Danielle M Dick; Fazil Aliev; Arpana Agrawal; Howard J Edenberg; John Kramer; John Nurnberger; Jay A Tischfield; Bernie Devlin; Robert E Ferrell; Galina P Kirillova; Ralph E Tarter; Kenneth S Kendler; Michael M Vanyukov Journal: Biol Psychiatry Date: 2011-04-22 Impact factor: 13.382
Authors: Arpana Agrawal; Neal D Freedman; Yu-Ching Cheng; Peng Lin; John R Shaffer; Qi Sun; Kira Taylor; Brian Yaspan; John W Cole; Marilyn C Cornelis; Rebecca S DeSensi; Annette Fitzpatrick; Gerardo Heiss; Jae H Kang; Jeffrey O'Connell; Siiri Bennett; Ebony Bookman; Kathleen K Bucholz; Neil Caporaso; Richard Crout; Danielle M Dick; Howard J Edenberg; Alison Goate; Victor Hesselbrock; Steven Kittner; John Kramer; John I Nurnberger; Lu Qi; John P Rice; Marc Schuckit; Rob M van Dam; Eric Boerwinkle; Frank Hu; Steven Levy; Mary Marazita; Braxton D Mitchell; Louis R Pasquale; Laura J Bierut Journal: Am J Clin Nutr Date: 2012-02-01 Impact factor: 7.045
Authors: Lingjun Zuo; Joel Gelernter; Clarence K Zhang; Hongyu Zhao; Lingeng Lu; Henry R Kranzler; Robert T Malison; Chiang-Shan R Li; Fei Wang; Xiang-Yang Zhang; Hong-Wen Deng; John H Krystal; Fengyu Zhang; Xingguang Luo Journal: Neuropsychopharmacology Date: 2011-09-28 Impact factor: 7.853