Chunk #27 — 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
receptor gene) 41 that were also found to be associated with alcohol dependence and related phenotypes (e.g., depression 104 ). These early genetic findings have been replicated and extended in several other samples throughout the world. 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 For example, in an independent sample of high‐risk offspring from multiplex AUD families, the association of variants within CHRM2 and P300 amplitude was confirmed, particularly trajectories of P300 in young male offspring aged 8–12. 115 Further, variation in GABRA2 (and its interaction with BDNF) was associated with gray matter volumes, suggesting that inherited variation in these genes may promote early developmental differences in neuronal proliferation of the cerebellum in these high‐risk offspring. 116 GABRA2 was also implicated in a large meta‐analytic genetic association study of EEG beta power and remained significant independent of COGA data. 117 In an independent sample, GRM8 variants were also found 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
