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Open AccessArticle

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

1
Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
2
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
3
Department of Psychology, Virginia Commonwealth University, Richmond, VA 23284, USA
4
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23284, USA
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Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
6
Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT 06030, USA
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Department of Psychiatry, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
8
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA
9
Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Newark, NJ 08901, USA
10
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
11
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
12
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
*
Author to whom correspondence should be addressed.
Brain Sci. 2019, 9(10), 280; https://doi.org/10.3390/brainsci9100280
Received: 30 July 2019 / Revised: 27 September 2019 / Accepted: 4 October 2019 / Published: 17 October 2019
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. View Full-Text
Keywords: AUD; AD; PRS; neural connectivity; EEG coherence; sex differences; developmental trajectories AUD; AD; PRS; neural connectivity; EEG coherence; sex differences; developmental trajectories
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Meyers, J.L.; Chorlian, D.B.; Johnson, E.C.; Pandey, A.K.; Kamarajan, C.; Salvatore, J.E.; Aliev, F.; Subbie-Saenz de Viteri, S.; Zhang, J.; Chao, M.; Kapoor, M.; Hesselbrock, V.; Kramer, J.; Kuperman, S.; Nurnberger, J.; Tischfield, J.; Goate, A.; Foroud, T.; Dick, D.M.; Edenberg, H.J.; Agrawal, A.; Porjesz, B. Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood. Brain Sci. 2019, 9, 280.

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