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Item Family-based Genome-wide Association Study of Frontal Theta Oscillations Identifies Potassium Channel Gene KCNJ6(Wiley, 2012) Kang, Sun J.; Rangaswamy, Madhavi; Manz, Niklas; Wang, Jen-Chyong; Wetherill, Leah; Hinrichs, Tony; Almasy, Laura; Brooks, Andy; Chorlian, David B.; Dick, Danielle; Hesselbrock, Victor; Kramer, John; Kuperman, Sam; Nurnberger, John, Jr.; Rice, John; Schuckit, Marc; Tischfield, Jay; Bierut, Laura J.; Edenberg, Howard J.; Goate, Alison; Foroud, Tatiana; Porjesz, Bernice; Psychiatry, School of MedicineEvent-related oscillations (EROs) represent highly heritable neuroelectric correlates of cognitive processes that manifest deficits in alcoholics and in offspring at high risk to develop alcoholism. Theta ERO to targets in the visual oddball task has been shown to be an endophenotype for alcoholism. A family-based genome-wide association study was performed for the frontal theta ERO phenotype using 634 583 autosomal single nucleotide polymorphisms (SNPs) genotyped in 1560 family members from 117 families densely affected by alcohol use disorders, recruited in the Collaborative Study on the Genetics of Alcoholism. Genome-wide significant association was found with several SNPs on chromosome 21 in KCNJ6 (a potassium inward rectifier channel; KIR3.2/GIRK2), with the most significant SNP at P = 4.7 × 10(-10)). The same SNPs were also associated with EROs from central and parietal electrodes, but with less significance, suggesting that the association is frontally focused. One imputed synonymous SNP in exon four, highly correlated with our top three SNPs, was significantly associated with the frontal theta ERO phenotype. These results suggest KCNJ6 or its product GIRK2 account for some of the variations in frontal theta band oscillations. GIRK2 receptor activation contributes to slow inhibitory postsynaptic potentials that modulate neuronal excitability, and therefore influence neuronal networks.Item Judgment in Older Adults with Normal Cognition, Cognitive Complaints, MCI, and Mild AD: Relation to Regional Frontal Gray Matter(Springer Nature, 2009) Rabin, Laura A.; Saykin, Andrew J.; West, John D.; Borgos, Marlana J.; Wishart, Heather A.; Nutter-Upham, Katherine E.; Flashman, Laura A.; Santulli, Robert B.; Radiology and Imaging Sciences, School of MedicineWe investigated regional gray matter (GM) reduction as a predictor of judgment ability in 120 non-depressed older adults with varying degrees of cognitive complaints and/or impairment (including those with MCI and mild AD). Participants underwent neuropsychological assessment, including the Test of Practical Judgment (TOP-J), a recently developed instrument that evaluates judgment and problem solving related to safety, medical, social/ethical, and financial issues. Structural MR scanning included T1-weighted SPGR volumes acquired at 1.5 Tesla. We used voxel-based morphometry to analyze the relationship between GM density and TOP-J scores, controlling for age, education, gender, intracranial volume, verbal memory, and crystallized knowledge. Consistent with our hypothesis, judgment ability correlated with GM density in prefrontal regions (left inferior and superior frontal gyri). Findings extend previous observations of frontal involvement in higher-order cognitive abilities/executive functions and provide initial validation of the TOP-J's sensitivity to the integrity of these brain regions in individuals at risk for dementia.