@article{3d46ad8e60d64cbd81669ae2d84dd298,
title = "Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures",
abstract = "Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples—the Study of Addictions: Genes and Environment (SAGE; n = 2336) and an Australian sample (OZ-ALC; n = 5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; 4110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.",
author = "M. Kapoor and Chou, {Y. L.} and Edenberg, {H. J.} and T. Foroud and Martin, {N. G.} and Madden, {P. A.F.} and Wang, {J. C.} and S. Bertelsen and L. Wetherill and A. Brooks and G. Chan and V. Hesselbrock and S. Kuperman and Medland, {S. E.} and G. Montgomery and J. Tischfield and Whitfield, {J. B.} and Bierut, {L. J.} and Heath, {A. C.} and Bucholz, {K. K.} and Goate, {A. M.} and A. Agrawal",
note = "Funding Information: LJB, AMG and JCW are listed as inventors on the patent 'Markers for Addiction' (US 20070258898) covering the use of certain SNPs in determining the diagnosis, prognosis and treatment of addiction. In addition, AA has previously received peer-reviewed grant funding and an honorarium from ABMRF/Foundation for Alcohol Research, which receives part of its funding from brewers. The remaining authors declare no conflicts of interest. Funding Information: AA and MK received support from, R21AA021235; AA receives support from K02DA32573. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01CA089392), and the Family Study of Cocaine Dependence (FSCD; R01DA013423, R01DA019963). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' (HHSN268200782096C). The Collaborative Study on the Genetics of Alcoholism (COGA): COGA, Principal Investigators B Porjesz, VH, HJE, LJB includes 10 different centers: the University of Connecticut (VH); the Indiana University (HJE, J Nurnberger Jr, TF); the University of Iowa (SK, J Kramer); SUNY Downstate (B Porjesz); the Washington University in Saint Louis (LJB, AMG, J Rice, KKB); the University of California at San Diego (M Schuckit); the Rutgers University (JT); the Southwest Foundation (L Almasy), the Howard University (R Taylor) and the 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 CoPI 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). OZ-ALC: Supported by NIH grants AA07535, AA07728, AA13320, AA13321, AA14041, AA11998, AA17688, DA012854, DA019951; by grants from the Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498); by grants from the Australian Research Council (A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921); and by the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254). GWAS genotyping at CIDR was supported by a grant to the late Richard Todd, former PI of grant AA13320 and a key contributor to research described in this manuscript. We acknowledge the contributions of project investigator Alexandre Todorov, at Washington University. We also thank Dixie Statham, Ann Eldridge, Marlene Grace, Kerrie McAloney (sample collection); Lisa Bowdler, Steven Crooks (DNA processing); David Smyth, Harry Beeby, and Daniel Park (IT support) at the Queensland Institute of Medical Research, Brisbane, Australia. Last, but not least, we thank the twins and their families for their participation. Publisher Copyright: {\textcopyright} 2016, Nature Publishing Group. All rights reserved.",
year = "2016",
doi = "10.1038/tp.2016.27",
language = "English",
volume = "6",
journal = "Translational psychiatry",
issn = "2158-3188",
number = "3",
}