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Int J Psychophysiol. 2017 May;115:98-111. doi: 10.1016/j.ijpsycho.2016.09.010. Epub 2016 Sep 23.

Genome-wide association study of working memory brain activation.

Author information

1
QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, 300 Herston Road, Brisbane, QLD, 4006, Australia; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia; School of Psychology, The University of Queensland, St Lucia, QLD, 4072, Australia. Electronic address: gabriella.blokland@uqconnect.edu.au.
2
QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, 300 Herston Road, Brisbane, QLD, 4006, Australia.
3
QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, 300 Herston Road, Brisbane, QLD, 4006, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, QLD, 4072, Australia.
4
Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, 2001 North Soto Street - Room 102, Marina del Rey, Los Angeles, CA 90032, United States.
5
Brain & Mind Research Institute, The University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia.
6
Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia.
7
School of Psychology, The University of Queensland, St Lucia, QLD, 4072, Australia; Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
8
QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, 300 Herston Road, Brisbane, QLD, 4006, Australia; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia; School of Psychology, The University of Queensland, St Lucia, QLD, 4072, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, QLD, 4072, Australia.

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.

KEYWORDS:

BOLD signal; Functional MRI; Genome-wide association study; Region-of-interest; Working memory; n-back

PMID:
27671502
PMCID:
PMC5364069
DOI:
10.1016/j.ijpsycho.2016.09.010
[Indexed for MEDLINE]
Free PMC Article

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