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

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

doi:10.3390/brainsci9100280

Abstract

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.

Highlights

Alcohol use disorder (AUD) results from a complex interaction of genetic and environmental liabilities across the lifespan [1]
Results from this study show that connectivity differences associated with polygenic risk scores (PRS) predate significant alcohol use, and sensitivity analyses did not detect a significant effect of drinking or DSM-5 alcohol use disorders (AUD) on the PRS-EEG
This is the first study to demonstrate the influence of polygenic risk for alcohol dependence on EEG coherence, an important marker of cognitive functioning and AUD, alongside neuropsychological performance, and lifetime alcohol and opioid use disorders

Summary

Introduction

Alcohol use disorder (AUD) results from a complex interaction of genetic and environmental liabilities across the lifespan [1]. Variations in brain structure and function are both antecedents to AUD and consequences of the effects of excessive alcohol consumption [2]. Given its exquisite temporal resolution (millisecond range), EEG coherence has proven to be a useful measure of neural connectivity patterns in specific. EEG frequency bands which, alongside clinical and fMRI data with spatial resolution allowing for anatomical specificity, can further our understanding of neural mechanisms of AUD [4]. Research characterizing genetic variation for AUD with respect to measures of neural connectivity can advance understanding of how genomic risk for AUD affects neurocognitive function. The number of large genome-wide association studies (GWAS) of alcohol-related behaviors has increased, covering a spectrum of phenotypes ranging from alcohol use to AUD diagnoses

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Discussion

Conclusion