Chunk #26 — 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
Our initial genetic studies took advantage of COGA's family history of AUD density and sensitive neurophysiological measures to perform linkage and association studies. We first reported significant linkage with resting EEG beta power and a GABAA receptor gene involved in inhibitory neural networks, 25 that was subsequently found to be associated with SNPs in GABRA2 and later with alcohol dependence, substance dependence, and related disorders, including precursor externalizing phenotypes. 100 , 101 , 102 These findings suggest an imbalance in excitation‐inhibition (hyperexcitability, disinhibition) in family members at risk for AUD. We identified several other genes in our COGA linkage families using neurophysiological phenotypes that were indices of risk for AUD. We found linkage and association between theta EROs to targets in the visual oddball task and SNPs in CHRM2 (cholinergic muscarinic receptor gene) 40 , 103 and GRM8 (metabotropic glutamate 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 ,
