In this study, we examined how PRS derived from a recent GWAS of DSM-IV AD [8] is associated with development of interhemispheric and intrahemispheric EEG coherence. AD PRS were associated with frontal-central, temporal-parietal, and parietal-occipital theta and alpha connectivity in adolescent and young adult COGA participants; this association was highly pronounced in males from ages 18–31, but not in females. Individuals with higher AD PRS also demonstrated deficits in neuropsychological performance, and increased risk for alcohol and opioid use disorders. When drinking frequency was controlled for, all associations remained statistically significant, indicating that the influence of the AD PRS on neural connectivity observed in this study is not primarily the effect of alcohol use on the brain. From these data, we conclude that measures of neural connectivity can be used to further understanding of how polygenic liability to AD may influence brain function, as well as the importance of examining sex and developmental effects in polygenic associations. We note however, that effect sizes were modest, ranging between 0.15 and 0.21 (beta coefficients ranged from 0.02–0.06), consistent with other developmental studies of EEG phenotypes [54,58].
