@article{950c1351138d4fe7b73cef38affbaecb,
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.",
keywords = "Age at onset, Alcohol dependence, GWAS, SNP, Survival analysis",
author = "Manav Kapoor and Wang, {Jen Chyong} and Leah Wetherill and Nhung Le and Sarah Bertelsen and Hinrichs, {Anthony L.} and John Budde and Arpana Agrawal and Laura Almasy and Kathleen Bucholz and Dick, {Danielle M.} and Oscar Harari and Xuei Xiaoling and Victor Hesselbrock and John Kramer and Nurnberger, {John I.} and John Rice and Marc Schuckit and Jay Tischfield and Bernice Porjesz and Edenberg, {Howard J.} and Laura Bierut and Tatiana Foroud and Alison Goate",
note = "Funding Information: The Collaborative Study on the Genetics of Alcoholism (COGA): This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Funding Information: The Collaborative Study on the Genetics of Alcoholism (COGA): COGA, Principal Investigators B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut includes ten different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr, T. Foroud); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz); Washington University in Saint Louis (L. Bierut, A. Goate, J. Rice, K. Bucholz); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield); Southwest Foundation (L. Almasy), Howard University (R. Taylor) and Virginia Commonwealth University (D. Dick). A. Parsian and M. Reilly are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, currently a consultant with COGA, P. Michael Conneally, Raymond Crowe and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). ",
year = "2014",
month = sep,
day = "1",
doi = "10.1016/j.drugalcdep.2014.05.023",
language = "English",
volume = "142",
pages = "56--62",
journal = "Drug and Alcohol Dependence",
issn = "0376-8716",
}