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- W2605302962 abstract "Highlights - We used voxel-level BOLD heritability to define region-of-interest phenotypes. - We performed genome-wide association on 20 n-back functional MRI BOLD phenotypes. - A BANK1 SNP explained 5.5% of variance in supramarginal gyrus n-back BOLD signal. - 31 independent SNPs were associated with BOLD signal change at p −5 . Abstract In a population-based genome-wide association (GWA) study of n-back working memory task-related brain activation, we extracted the average percent BOLD signal change (2-back minus 0-back) from 46 regions-of-interest (ROIs) in functional MRI scans from 863 healthy twins and siblings. ROIs were obtained by creating spheres around group random effects analysis local maxima, and by thresholding a voxel-based heritability map of working memory brain activation at 50%. Quality control for test-retest reliability and heritability of ROI measures yielded 20 reliable (r > 0.7) and heritable (h 2 > 20%) ROIs. For GWA analysis, the cohort was divided into a discovery (n = 679) and replication (n = 97) sample. No variants survived the stringent multiple-testing-corrected genome-wide significance threshold (p −9 ), or were replicated (p −5 . Two SNPs (rs7917410 and rs7672408) were associated at a significance level of p −7 . Only one, most strongly affecting BOLD signal change in the left supramarginal gyrus (R 2 = 5.5%), had multiple SNPs associated at p −5 in linkage disequilibrium with it, all located in and around the BANK1 gene. BANK1 encodes a B-cell-specific scaffold protein and has been shown to negatively regulate CD40-mediated AKT activation. AKT is part of the dopamine-signaling pathway, suggesting a mechanism for the involvement of BANK1 in the BOLD response to working memory. Variants identified here may be relevant to (the susceptibility to) common disorders affecting brain function." @default.
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- W2605302962 date "2017-01-01" @default.
- W2605302962 modified "2023-09-26" @default.
- W2605302962 title "Genome-wide association study of working memory brain activation" @default.
- W2605302962 hasPublicationYear "2017" @default.
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