Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
27671502
TITLE
Genome-wide association study of working memory brain activation.
ABSTRACT
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.
DATE PUBLISHED
2016 Sep 23
HISTORY
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
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Blokland GA Blokland Gabriëlla A M GA 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 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 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 Brain & Mind Research Institute, The University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, 300 Herston Road, Brisbane, QLD, 4006, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, 300 Herston Road, Brisbane, QLD, 4006, Australia.
McMahon KL McMahon Katie L KL Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia.
de Zubicaray GI de Zubicaray Greig I GI 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 Wright Margaret J MJ 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.
INVESTIGATORS
JOURNAL
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
MEDLINE JOURNAL
MEDLINETA: Int J Psychophysiol
COUNTRY: Netherlands
ISSNLINKING: 0167-8760
NLMUNIQUEID: 8406214
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
JOURNAL ARTICLE
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
BOLD signal
Functional MRI
Genome-wide association study
Region-of-interest
Working memory
n-back
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's