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

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.

Predicting alcohol-related memory problems in older adults: A machine learning study with multi-domain features

“…Recently, Lai et al [67] reported that individuals with AUD had higher PRS than controls and the PRS magnitude increased as the number of DSM-5 diagnostic criteria increased. Further, PRS for alcohol dependence was found to be associated with neural connectivity [36, 157] and cognitive functions, such as verbal fluency, vocabulary, digit-symbol coding, and logical memory [158], as well as brain structure [159]. Unfortunately, PRS related to neurocognitive phenotypes, which could have improved the predictive model, were not included in the study due to a lack of neurocognitive GWAS on AA populations for calculating PRS-CSx for the study sample.…”

Alcohol drinking and alcohol use disorder across the ages: Dynamic effects on the brain and function.

“…Machine learning studies support the role of brain functions and structures to determine the profiles of and risk factors for alcohol misuse among adolescents and young adults (Gowin et al, 2021;Ruan et al, 2019;Whelan et al, 2014) and indicate roles for early drinking onset, family history of AUD, and stressful life events. Critically, longitudinal studies showed that childhood trauma predicts binge drinking (De Bellis et al, 2020), alcohol-related problems (Hagborg et al, 2020), disturbed brain FC (Silveira et al, 2020), and neural oscillations (Meyers et al, 2019). An underappreciated caveat in longitudinal performance testing is a learning effect, also known as the prior testing experience effect (Salthouse, 2014), which needs to be quantified in the context of change expected from developmental advancement (Sullivan et al, 2017).…”

Reaction Time and Visual Memory in Connection to Hazardous Drinking Polygenic Scores in Schizophrenia, Schizoaffective Disorder and Bipolar Disorder

“…In normal population studies, PGS for alcohol dependence has been found to be negatively associated with cognitive function [3,4]. No evidence was found for a causal association of cognitive impairment for rs1229984 in Alcohol Dehydrogenase 1B (ADH1B) [5,6] ( Almeida et al 2014, Kumari M et al 2014 or rs671 in Alcohol Dehydrogenase 2 (ALDH2) [7] in the normal population [8].…”