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| PMID |
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| TITLE |
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| Genome-wide association study of working memory brain activation. |
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| ABSTRACT |
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NlmCategory: UNASSIGNED |
| 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<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 (R(2)=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. |
| Copyright © 2016. Published by Elsevier B.V. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2015/10/06 |
| revised |
2016/08/05 |
| accepted |
2016/09/15 |
| entrez |
2016/09/28 06:00 |
| pubmed |
2016/09/28 06:00 |
| medline |
2016/09/28 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Blokland GA |
|
Blokland |
Gabriëlla A M |
GA |
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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. |
| Wallace AK |
|
Wallace |
Angus K |
AK |
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QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, 300 Herston Road, Brisbane, QLD, 4006, Australia. |
| Hansell NK |
|
Hansell |
Narelle K |
NK |
|
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. |
| Thompson PM |
|
Thompson |
Paul M |
PM |
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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. |
| Hickie IB |
|
Hickie |
Ian B |
IB |
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Brain & Mind Research Institute, The University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
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QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, 300 Herston Road, Brisbane, QLD, 4006, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, 300 Herston Road, Brisbane, QLD, 4006, Australia. |
| McMahon KL |
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McMahon |
Katie L |
KL |
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Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia. |
| de Zubicaray GI |
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de Zubicaray |
Greig I |
GI |
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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. |
| Wright MJ |
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Wright |
Margaret J |
MJ |
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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. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: International journal of psychophysiology : official journal of the International Organization of Psychophysiology |
| ISOABBREVIATION: Int J Psychophysiol |
| YEAR: 2016 |
| MONTH: Sep |
| DAY: 23 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1872-7697 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Int J Psychophysiol |
| COUNTRY: Netherlands |
| ISSNLINKING: 0167-8760 |
| NLMUNIQUEID: 8406214 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| JOURNAL ARTICLE |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| BOLD signal |
| Functional MRI |
| Genome-wide association study |
| Region-of-interest |
| Working memory |
| n-back |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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