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Drug Alcohol Depend. 2014 Sep 1;142:56-62. doi: 10.1016/j.drugalcdep.2014.05.023. Epub 2014 Jun 11.

Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families.

Author information

1
Washington University School of Medicine, United States.
2
Indiana University School of Medicine, United States.
3
Southwest Foundation for Biomedical Research, United States.
4
Virginia Commonwealth University, United States.
5
University of Connecticut Health Center, United States.
6
University of Iowa Carver College of Medicine, United States.
7
University of California, San Diego, United States.
8
Rutgers University, United States.
9
SUNY Health Sciences Center, United States.
10
Washington University School of Medicine, United States. Electronic address: goate@wustl.edu.

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.

KEYWORDS:

Age at onset; Alcohol dependence; GWAS; SNP; Survival analysis

PMID:
24962325
PMCID:
PMC4127128
DOI:
10.1016/j.drugalcdep.2014.05.023
[Indexed for MEDLINE]
Free PMC Article

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