title: Genome-wide association study of alcohol dependence implicates a region on chromosome 11.
abstract: 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.affiliation: Department of Biochemistry, Indiana University School of Medicine, Indianapolis, 46202-5122, USA. edenberg@iupui.edu <edenberg@iupui.edu>
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xuei
authors.forename: Leah
authors.initials: L
authors.lastname: Wetherill
authors.forename: Jeanette N
authors.initials: JN
authors.lastname: McClintick
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Bucholz
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Fazil
authors.initials: F
authors.lastname: Aliev
authors.forename: Danielle
authors.initials: D
authors.lastname: Dick
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: Anthony
authors.initials: A
authors.lastname: Hinrichs
authors.forename: John
authors.initials: J
authors.lastname: Kramer
authors.forename: Sam
authors.initials: S
authors.lastname: Kuperman
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schuckit
authors.forename: Robert
authors.initials: R
authors.lastname: Taylor
authors.forename: B
authors.initials: B
authors.lastname: Todd Webb
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
mesh_terms: D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods* / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult