Genome-wide association studies of the self-rating of effects of ethanol (SRE)

Dongbing Lai¹, Leah Wetherill¹, Manav Kapoor², Emma C Johnson³, Melanie Schwandt⁴, Vijay A Ramchandani⁵, David Goldman⁴, Geoff Joslyn⁶, Xi Rao¹, Yunlong Liu¹, Sean Farris⁷, R Dayne Mayfield⁷, Danielle Dick⁸, Victor Hesselbrock⁹, John Kramer¹⁰, Vivia V McCutcheon³, John Nurnberger^{1

11}, Jay Tischfield¹², Alison Goate², Howard J Edenberg^{1

13}, Bernice Porjesz¹⁴, Arpana Agrawal³, Tatiana Foroud¹, Marc Schuckit¹⁵

Affiliations

¹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
² Department of Neuroscience, Icahn School of Medicine at Mt. Sinai, New York, New York.
³ Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
⁴ Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
⁵ Section on Human Psychopharmacology, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
⁶ Ernest Gallo Clinic and Research Center, Emeryville, California.
⁷ Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas.
⁸ Department of Psychology, Virginia Commonwealth University, Richmond, Virginia.
⁹ Department of Psychiatry, University of Connecticut, Farmington, Connecticut.
¹⁰ Department of Psychiatry, Roy Carver College of Medicine, University of Iowa, Iowa City, Iowa.
¹¹ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana.
¹² Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, New Jersey.
¹³ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
¹⁴ Henri Begleiter Neurodynamics Lab, Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, New York.
¹⁵ Department of Psychiatry, University of California, San Diego Medical School, San Diego, California.

PMID: 31270906
PMCID: PMC6940552
DOI: 10.1111/adb.12800

Meta-Analysis

Genome-wide association studies of the self-rating of effects of ethanol (SRE)

Dongbing Lai et al. Addict Biol. 2020 Mar.

. 2020 Mar;25(2):e12800.

doi: 10.1111/adb.12800. Epub 2019 Jul 3.

Authors

Affiliations

¹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
² Department of Neuroscience, Icahn School of Medicine at Mt. Sinai, New York, New York.
³ Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
⁴ Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
⁵ Section on Human Psychopharmacology, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
⁶ Ernest Gallo Clinic and Research Center, Emeryville, California.
⁷ Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas.
⁸ Department of Psychology, Virginia Commonwealth University, Richmond, Virginia.
⁹ Department of Psychiatry, University of Connecticut, Farmington, Connecticut.
¹⁰ Department of Psychiatry, Roy Carver College of Medicine, University of Iowa, Iowa City, Iowa.
¹¹ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana.
¹² Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, New Jersey.
¹³ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
¹⁴ Henri Begleiter Neurodynamics Lab, Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, New York.
¹⁵ Department of Psychiatry, University of California, San Diego Medical School, San Diego, California.

PMID: 31270906
PMCID: PMC6940552
DOI: 10.1111/adb.12800

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 (r_g : 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).

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References

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Genome-wide association studies of the self-rating of effects of ethanol (SRE)

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Genome-wide association studies of the self-rating of effects of ethanol (SRE)

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