Chunk #30 — 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? — Genome‐wide association studies (GWAS) of neurophysiological phenotypes
Genetic data from COGA's enriched and ancestrally diverse families have been used independently as well as in consortia efforts (e.g., ENIGMA‐EEG) to conduct GWAS of the EEG‐based phenotypes described in Table 2. In one example, a family‐based GWAS of frontal theta EROs during P300 to targets in the visual oddball task identified several genome‐wide significant non‐coding variants as well as a synonymous SNP (rs702859) within KCNJ6 (the gene encoding GIRK2, G protein‐activated inward rectifier potassium channel 2). 42 Converging data from other research groups has demonstrated that GIRK2 activation contributes to slow inhibitory postsynaptic potentials important in modulating neuronal excitability. GIRK channels are directly activated by ethanol 124 and play an important role in both ethanol‐ and opioid‐induced analgesia. Low frontal theta ERO activation is associated with AUD 35 and those at risk, 36 and these genetic findings suggest that GIRK2 activation accounts for some of the variations in frontal theta oscillations seen in COGA families. We used COGA's longitudinal data to examine the neurodevelopmental trajectories of these frontal theta ERO phenotypes in the same visual oddball task during adolescence
