Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood

Jacquelyn  L. Meyers; David  B. Chorlian; Emma  C. Johnson; Ashwini  K. Pandey; Chella Kamarajan; Jessica  E. Salvatore; Fazil Aliev; Stacey Subbie-Saenz de Viteri; Jian Zhang; Michael Chao; Manav Kapoor; Victor Hesselbrock; John Kramer; Samuel Kuperman; John Nurnberger; Jay Tischfield; Alison Goate; Tatiana Foroud; Danielle  M. Dick; Howard  J. Edenberg; Arpana Agrawal; Bernice Porjesz

doi:10.3390/brainsci9100280

Brain Sciences (Oct 2019)

Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood

Jacquelyn L. Meyers,
David B. Chorlian,
Emma C. Johnson,
Ashwini K. Pandey,
Chella Kamarajan,
Jessica E. Salvatore,
Fazil Aliev,
Stacey Subbie-Saenz de Viteri,
Jian Zhang,
Michael Chao,
Manav Kapoor,
Victor Hesselbrock,
John Kramer,
Samuel Kuperman,
John Nurnberger,
Jay Tischfield,
Alison Goate,
Tatiana Foroud,
Danielle M. Dick,
Howard J. Edenberg,
Arpana Agrawal,
Bernice Porjesz

Affiliations

Jacquelyn L. Meyers: Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
David B. Chorlian: Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
Emma C. Johnson: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
Ashwini K. Pandey: Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
Chella Kamarajan: Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
Jessica E. Salvatore: Department of Psychology, Virginia Commonwealth University, Richmond, VA 23284, USA
Fazil Aliev: Department of Psychology, Virginia Commonwealth University, Richmond, VA 23284, USA
Stacey Subbie-Saenz de Viteri: Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
Jian Zhang: Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
Michael Chao: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Manav Kapoor: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Victor Hesselbrock: Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT 06030, USA
John Kramer: Department of Psychiatry, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Samuel Kuperman: Department of Psychiatry, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
John Nurnberger: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Jay Tischfield: Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Newark, NJ 08901, USA
Alison Goate: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Tatiana Foroud: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Danielle M. Dick: Department of Psychology, Virginia Commonwealth University, Richmond, VA 23284, USA
Howard J. Edenberg: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Arpana Agrawal: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
Bernice Porjesz: Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA

DOI: https://doi.org/10.3390/brainsci9100280
Journal volume & issue: Vol. 9, no. 10
p. 280

Abstract

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Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18−31 (beta coefficients ranged from 0.02−0.06, p-values ranged from 10−6−10−12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective.

Published in Brain Sciences

ISSN: 2076-3425 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.mdpi.com/journal/brainsci/

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