@article{956502e8511c434fa1d64d7ea6070014,
title = "Genome-wide association studies of the self-rating of effects of ethanol (SRE)",
abstract = "The level of response (LR) to alcohol as measured with the Self-Report of the Effects of Alcohol Retrospective Questionnaire (SRE) evaluates the number of standard drinks usually required for up to four effects. The need for a higher number of drinks for effects is genetically influenced and predicts higher risks for heavy drinking and alcohol problems. We conducted genome-wide association study (GWAS) in the African-American (COGA-AA, N = 1527 from 309 families) and European-American (COGA-EA, N = 4723 from 956 families) subsamples of the Collaborative Studies on the Genetics of Alcoholism (COGA) for two SRE scores: SRE-T (average of first five times of drinking, the period of heaviest drinking, and the most recent 3 months of consumption) and SRE-5 (the first five times of drinking). We then meta-analyzed the two COGA subsamples (COGA-AA + EA). Both SRE-T and SRE-5 were modestly heritable (h2: 21%-31%) and genetically correlated with alcohol dependence (AD) and DSM-IV AD criterion count (rg: 0.35-0.76). Genome-wide significant associations were observed (SRE-T: chromosomes 6, rs140154945, COGA-EA P = 3.30E-08 and 11, rs10647170, COGA-AA+EA P = 3.53E-09; SRE-5: chromosome13, rs4770359, COGA-AA P = 2.92E-08). Chromosome 11 was replicated in an EA dataset from the National Institute on Alcohol Abuse and Alcoholism intramural program. In silico functional analyses and RNA expression analyses suggest that the chromosome 6 locus is an eQTL for KIF25. Polygenic risk scores derived using the COGA SRE-T and SRE-5 GWAS predicted 0.47% to 2.48% of variances in AD and DSM-IV AD criterion count in independent datasets. This study highlights the genetic contribution of alcohol response phenotypes to the etiology of alcohol use disorders.",
keywords = "RNA expression, genetic correlation, genome-wide association study (GWAS), heritability, polygenic risk score, self-rating of the effects of ethanol (SRE)",
author = "Dongbing Lai and Leah Wetherill and Manav Kapoor and Johnson, {Emma C.} and Melanie Schwandt and Ramchandani, {Vijay A.} and David Goldman and Geoff Joslyn and Xi Rao and Yunlong Liu and Sean Farris and Mayfield, {R. Dayne} and Danielle Dick and Victor Hesselbrock and John Kramer and McCutcheon, {Vivia V.} and John Nurnberger and Jay Tischfield and Alison Goate and Edenberg, {Howard J.} and Bernice Porjesz and Arpana Agrawal and Tatiana Foroud and Marc Schuckit",
note = "Funding Information: COGA: The Collaborative Study on the Genetics of Alcoholism (COGA), principal investigators B.P., V.H., H.E., L.B., includes 11 different centers: University of Connecticut (V.H.); Indiana University (H.J.E., J.N. Jr., T.F., and Y. L.); University of Iowa (S.K. and J.K.); SUNY Downstate (B.P.); Washington University in St. Louis (L.B., J.R., K.B., and A.A.); University of California at San Diego (M.S.); Rutgers University (J.T. and A.B.); Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA (L.A.), Virginia Commonwealth University (D.D.), Icahn School of Medicine at Mount Sinai (A.G.), and Howard University (R.T.). Other COGA collaborators include: L.B. (University of Connecticut); J.M., L.W., X.X., D.L., S.O'C., M.P., S.L. (Indiana University); G.C. (University of Iowa; University of Connecticut); J.M, D.C., C.K., A.P., J.Z. (SUNY Downstate); J.-C.W., M.K., S.B. (Icahn School of Medicine at Mount Sinai); A.A., V.M., S.S. (Washington University); J.S., F.A., B.C. (Virginia Commonwealth University); and M.K. (University of Texas Rio Grande Valley). A.P. and H.C. 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, 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). Funding Information: COGA is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). A. Agrawal receives additional funding support from NIDA (DA032573). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268201200008I. D. Goldman, M.L. Schwandt, and V.A. Ramchandani are supported by the NIAAA Division of Intramural Clinical and Biological Research. R. Dayne Mayfield is supported from NIH/NIAAA: AA020926 and AA012404. Alison Goate is listed as an inventor on issued U.S. Patent 8080,371, “Markers for Addiction” covering the use of certain variants in determining the diagnosis, prognosis, and treatment of addiction. John Nurnberger receives support as an investigator for Janssen. All other authors have no potential conflicts of interest. Funding Information: 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, 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). Publisher Copyright: {\textcopyright} 2019 Society for the Study of Addiction",
year = "2020",
month = mar,
day = "1",
doi = "10.1111/adb.12800",
language = "English (US)",
volume = "25",
journal = "Addiction Biology",
issn = "1355-6215",
publisher = "Wiley-Blackwell",
number = "2",
}