title: Genome-wide association study of alcohol dependence.
abstract: BACKGROUND
  Alcohol dependence is a serious and common public health problem. It is well established that genetic factors play a major role in the development of this disorder. Identification of genes that contribute to alcohol dependence will improve our understanding of the mechanisms that underlie this disorder.
  
  
  OBJECTIVE
  To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and a follow-up study in a population of German male inpatients with an early age at onset.
  
  
  METHODS
  The GWAS tested 524,396 single-nucleotide polymorphisms (SNPs). All SNPs with P < 10(-4) were subjected to the follow-up study. In addition, nominally significant SNPs from genes that had also shown expression changes in rat brains after long-term alcohol consumption were selected for the follow-up step.
  
  
  METHODS
  Five university hospitals in southern and central Germany.
  
  
  METHODS
  The GWAS included 487 male inpatients with alcohol dependence as defined by the DSM-IV and an age at onset younger than 28 years and 1358 population-based control individuals. The follow-up study included 1024 male inpatients and 996 age-matched male controls. All the participants were of German descent.
  
  
  METHODS
  Significant association findings in the GWAS and follow-up study with the same alleles.
  
  
  RESULTS
  The GWAS produced 121 SNPs with nominal P < 10(-4). These, together with 19 additional SNPs from homologues of rat genes showing differential expression, were genotyped in the follow-up sample. Fifteen SNPs showed significant association with the same allele as in the GWAS. In the combined analysis, 2 closely linked intergenic SNPs met genome-wide significance (rs7590720, P = 9.72 x 10(-9); rs1344694, P = 1.69 x 10(-8)). They are located on chromosome region 2q35, which has been implicated in linkage studies for alcohol phenotypes. Nine SNPs were located in genes, including the CDH13 and ADH1C genes, that have been reported to be associated with alcohol dependence.
  
  
  CONCLUSIONS
  This is the first GWAS and follow-up study to identify a genome-wide significant association in alcohol dependence. Further independent studies are required to confirm these findings.
authors: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
authors: Jens
authors: J
authors: Treutlein
authors: Sven
authors: S
authors: Cichon
authors: Monika
authors: M
authors: Ridinger
authors: Norbert
authors: N
authors: Wodarz
authors: Michael
authors: M
authors: Soyka
authors: Peter
authors: P
authors: Zill
authors: Wolfgang
authors: W
authors: Maier
authors: Rainald
authors: R
authors: Moessner
authors: Wolfgang
authors: W
authors: Gaebel
authors: Norbert
authors: N
authors: Dahmen
authors: Christoph
authors: C
authors: Fehr
authors: Norbert
authors: N
authors: Scherbaum
authors: Michael
authors: M
authors: Steffens
authors: Kerstin U
authors: KU
authors: Ludwig
authors: Josef
authors: J
authors: Frank
authors: H Erich
authors: HE
authors: Wichmann
authors: Stefan
authors: S
authors: Schreiber
authors: Nico
authors: N
authors: Dragano
authors: Wolfgang H
authors: WH
authors: Sommer
authors: Fernando
authors: F
authors: Leonardi-Essmann
authors: Anbarasu
authors: A
authors: Lourdusamy
authors: Peter
authors: P
authors: Gebicke-Haerter
authors: Thomas F
authors: TF
authors: Wienker
authors: Patrick F
authors: PF
authors: Sullivan
authors: Markus M
authors: MM
authors: Nöthen
authors: Falk
authors: F
authors: Kiefer
authors: Rainer
authors: R
authors: Spanagel
authors: Karl
authors: K
authors: Mann
authors: Marcella
authors: M
authors: Rietschel
mesh_terms: D000328:Adult; D017668:Age of Onset; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000430:Alcohol Withdrawal Delirium / Q000235:genetics / Q000534:rehabilitation; D000437:Alcoholism / Q000235:genetics* / Q000534:rehabilitation; D000483:Alleles; D000679:Amygdala / Q000473:pathology; D000818:Animals; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000473:pathology; D002889:Chromosomes, Human, Pair 2; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006760:Hospitalization; D006801:Humans; D008126:Lod Score; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011699:Putamen / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D055815:Young Adult
chemical_list: D015820:Cadherins; D005819:Genetic Markers; C099972:H-cadherin; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase