Genome-wide association study of working memory brain activation

Blokland, Gabriella A. M., Wallace, Angus K., Hansell, Narelle K., Thompson, Paul M., Hickie, Ian B., Montgomery, Grant W., Martin, Nicholas G., McMahon, Katie L., de Zubicaray, Greig I. and Wright, Margaret J. (2016) Genome-wide association study of working memory brain activation. International Journal of Psychophysiology, 115 98-111. doi:10.1016/j.ijpsycho.2016.09.010


Author Blokland, Gabriella A. M.
Wallace, Angus K.
Hansell, Narelle K.
Thompson, Paul M.
Hickie, Ian B.
Montgomery, Grant W.
Martin, Nicholas G.
McMahon, Katie L.
de Zubicaray, Greig I.
Wright, Margaret J.
Title Genome-wide association study of working memory brain activation
Journal name International Journal of Psychophysiology   Check publisher's open access policy
ISSN 1872-7697
0167-8760
Publication date 2016-09-23
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.ijpsycho.2016.09.010
Open Access Status Not yet assessed
Volume 115
Start page 98
End page 111
Total pages 14
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 2800 Neuroscience
3206 Neuropsychology and Physiological Psychology
2737 Physiology (medical)
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 > 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 < 4.5 × 10), or were replicated (p < 0.0016), but several genes were identified that are worthy of further investigation. A search of 529,379 genomic markers resulted in discovery of 31 independent single nucleotide polymorphisms (SNPs) associated with BOLD signal change at a discovery level of p < 1 × 10. Two SNPs (rs7917410 and rs7672408) were associated at a significance level of p < 1 × 10. Only one, most strongly affecting BOLD signal change in the left supramarginal gyrus (R = 5.5%), had multiple SNPs associated at p < 1 × 10 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.
Formatted 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 (h2 > 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 < 4.5 × 10−9), or were replicated (p < 0.0016), but several genes were identified that are worthy of further investigation. A search of 529,379 genomic markers resulted in discovery of 31 independent single nucleotide polymorphisms (SNPs) associated with BOLD signal change at a discovery level of p < 1 × 10−5. Two SNPs (rs7917410 and rs7672408) were associated at a significance level of p < 1 × 10−7. Only one, most strongly affecting BOLD signal change in the left supramarginal gyrus (R2 = 5.5%), had multiple SNPs associated at p < 1 × 10−5 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.
Keyword Genome-wide association study
n-back
Working memory
Functional MRI
BOLD signal
Region-of-interest
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R01 HD050735
496682
CT-10803
FT0991634
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
School of Psychology Publications
Centre for Advanced Imaging Publications
 
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Created: Wed, 15 Feb 2017, 16:04:37 EST by Kirstie Asmussen on behalf of Centre for Advanced Imaging