Chunk #28 — HOW DO NEURAL SIGNATURES ASSOCIATED WITH AUD HELP ELUCIDATE THE ROLE OF BRAIN FUNCTION IN THE RISK AND CONSEQUENCES OF ALCOHOL USE AND AUD ACROSS THE LIFESPAN? — How do genomic factors influence brain functioning across the lifespan and contribute to antecedents and resilience for AUD? — Early linkage and association studies of neurophysiological (endo)phenotypes
to be associated with P300 amplitude during response inhibition, as well as with AUD and related disorders, with data suggesting that the association of GRM8 and AUD may be mediated through an inherited instability in brain function that affects cognitive control. 118 These early studies are still being evaluated in much larger GWAS studies of alcohol dependence and related phenotypes. We also found that increased interhemispheric resting state EEG coherence in AUD families, suggesting dysfunctional thalamo‐cortical and cortico‐cortical connectivity. 28 This measure of coherence was significantly associated with SNPs in GABRA2 at parieto‐occipital regions and SNPs in CHRM2 at centro‐parietal regions. The GABAergic and cholinergic systems interact in local inhibitory circuits, and therefore are likely to impact cortical synchronization (i.e., coherence), which animal models suggest may impair behavioral flexibility and contribute to memory deficits. 119 These early findings are now emerging in much larger GWAS studies of alcohol dependence and related phenotypes. For example, variants in GABRA2, CHRM2 and GRM8 have been implicated in large GWAS (>1 million participants) of alcohol consumption, risk‐taking behaviors, and related addictive phenotypes 120 , 121 , 122 (e.g., smoking). Variants in GABRA2 have also been associated with EEG‐based phenotypes, 123 but in relatively smaller
