COGA's brain function data (see, 3. Brain Function) have also been paired with the project's functional genomics pipeline (see, 5. Functional Genomics) to provide mechanistic insights. In an example of this, several variants within KCNJ6 (encoding the GIRK2 G‐protein coupled inwardly rectifying potassium channel) were identified as genome‐wide significant in our family‐based GWAS of a frontal theta EEG phenotype 75 (an endophenotype for AUD 14 ). The role of KCNJ6 in alcohol‐ and other reward‐related behaviors is supported by multiple independent studies. 100 , 101 , 102 , 103 , 104 , 105 Pursuing this gene using iPSC derived neurons and lymphocytes from COGA participants with and without AUD, we recently showed that neurons derived from AUD COGA subjects express lower levels of GIRK2 and that exposure to levels of ethanol consistent with the human phenotype of intoxication reverses these functional effects 100 (see, 5. Functional Genomics).
