title: Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families.
abstract: BACKGROUND
  The age at onset of alcohol dependence (AD) is a critical moderator of genetic associations for alcohol dependence. The present study evaluated whether single nucleotide polymorphisms (SNPs) can influence the age at onset of AD in large high-risk families from the Collaborative Study on the Genetics of Alcoholism (COGA).
  
  
  METHODS
  Genomewide SNP genotyping was performed in 1788 regular drinkers from 118 large European American families densely affected with alcoholism. We used a genome-wide Cox proportional hazards regression model to test for association between age at onset of AD and SNPs.
  
  
  RESULTS
  This family-based analysis identified an intergenic SNP, rs2168784 on chromosome 3 that showed strong evidence of association (P=5×10(-9)) with age at onset of AD among regular drinkers. Carriers of the minor allele of rs2168784 had 1.5 times the hazard of AD onset as compared with those homozygous for the major allele. By the age of 20 years, nearly 30% of subjects homozygous for the minor allele were alcohol dependent while only 19% of those homozygous for the major allele were. We also identified intronic SNPs in the ADP-ribosylation factor like 15 (ARL15) gene on chromosome 5 (P=1.11×10(-8)) and the UTP20 small subunit (UTP20) gene on chromosome 12 (P=4.32×10(-8)) that were associated with age at onset of AD.
  
  
  CONCLUSIONS
  This extended family based genome-wide cox-proportional hazards analysis identified several loci that might be associated with age at onset of AD.
authors: Washington University School of Medicine, United States.
authors: Manav
authors: M
authors: Kapoor
authors: Washington University School of Medicine, United States.
authors: Jen-Chyong
authors: JC
authors: Wang
authors: Indiana University School of Medicine, United States.
authors: Leah
authors: L
authors: Wetherill
authors: Washington University School of Medicine, United States.
authors: Nhung
authors: N
authors: Le
authors: Washington University School of Medicine, United States.
authors: Sarah
authors: S
authors: Bertelsen
authors: Washington University School of Medicine, United States.
authors: Anthony L
authors: AL
authors: Hinrichs
authors: Washington University School of Medicine, United States.
authors: John
authors: J
authors: Budde
authors: Washington University School of Medicine, United States.
authors: Arpana
authors: A
authors: Agrawal
authors: Southwest Foundation for Biomedical Research, United States.
authors: Laura
authors: L
authors: Almasy
authors: Washington University School of Medicine, United States.
authors: Kathleen
authors: K
authors: Bucholz
authors: Virginia Commonwealth University, United States.
authors: Danielle M
authors: DM
authors: Dick
authors: Washington University School of Medicine, United States.
authors: Oscar
authors: O
authors: Harari
authors: Indiana University School of Medicine, United States.
authors: Xuei
authors: X
authors: Xiaoling
authors: University of Connecticut Health Center, United States.
authors: Victor
authors: V
authors: Hesselbrock
authors: University of Iowa Carver College of Medicine, United States.
authors: John
authors: J
authors: Kramer
authors: Indiana University School of Medicine, United States.
authors: John I
authors: JI
authors: Nurnberger
authors: Washington University School of Medicine, United States.
authors: John
authors: J
authors: Rice
authors: University of California, San Diego, United States.
authors: Marc
authors: M
authors: Schuckit
authors: Rutgers University, United States.
authors: Jay
authors: J
authors: Tischfield
authors: SUNY Health Sciences Center, United States.
authors: Bernice
authors: B
authors: Porjesz
authors: Indiana University School of Medicine, United States.
authors: Howard J
authors: HJ
authors: Edenberg
authors: Washington University School of Medicine, United States.
authors: Laura
authors: L
authors: Bierut
authors: Indiana University School of Medicine, United States.
authors: Tatiana
authors: T
authors: Foroud
authors: Washington University School of Medicine, United States. Electronic address: goate@wustl.edu.
authors: Alison
authors: A
authors: Goate
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D055815:Young Adult
keywords: Age at onset; Alcohol dependence; GWAS; SNP; Survival analysis