Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
25264344
TITLE
Genome-wide interaction analysis reveals replicated epistatic effects on brain structure.
ABSTRACT
The discovery of several genes that affect the risk for Alzheimer's disease ignited a worldwide search for single-nucleotide polymorphisms (SNPs), common genetic variants that affect the brain. Genome-wide search of all possible SNP-SNP interactions is challenging and rarely attempted because of the complexity of conducting approximately 10(11) pairwise statistical tests. However, recent advances in machine learning, for example, iterative sure independence screening, make it possible to analyze data sets with vastly more predictors than observations. Using an implementation of the sure independence screening algorithm (called EPISIS), we performed a genome-wide interaction analysis testing all possible SNP-SNP interactions affecting regional brain volumes measured on magnetic resonance imaging and mapped using tensor-based morphometry. We identified a significant SNP-SNP interaction between rs1345203 and rs1213205 that explains 1.9% of the variance in temporal lobe volume. We mapped the whole brain, voxelwise effects of the interaction in the Alzheimer's Disease Neuroimaging Initiative data set and separately in an independent replication data set of healthy twins (Queensland Twin Imaging). Each additional loading in the interaction effect was associated with approximately 5% greater brain regional brain volume (a protective effect) in both Alzheimer's Disease Neuroimaging Initiative and Queensland Twin Imaging samples.
Copyright © 2015 Elsevier Inc. All rights reserved.
DATE PUBLISHED
2015 Jan
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/05/02
revised 2014/02/10
accepted 2014/02/16
aheadofprint 2014/08/27
entrez 2014/09/30 06:00
pubmed 2014/09/30 06:00
medline 2015/08/28 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hibar DP Hibar Derrek P DP Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Stein JL Stein Jason L JL Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Jahanshad N Jahanshad Neda N Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Kohannim O Kohannim Omid O Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Hua X Hua Xue X Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Toga AW Toga Arthur W AW Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
McMahon KL McMahon Katie L KL Centre for Magnetic Resonance, School of Psychology, University of Queensland, Brisbane, Queensland, Australia.
de Zubicaray GI de Zubicaray Greig I GI Functional Magnetic Resonance Imaging Laboratory, School of Psychology, University of Queensland, Brisbane, Queensland, Australia.
Martin NG Martin Nicholas G NG Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
Wright MJ Wright Margaret J MJ Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
Alzheimer's Disease Neuroimaging Initiative
Weiner MW Weiner Michael W MW Department of Radiology, UC San Francisco, San Francisco, CA, USA; Department of Medicine, UC San Francisco, San Francisco, CA, USA; Department of Psychiatry, UC San Francisco, San Francisco, CA, USA; Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
Thompson PM Thompson Paul M PM Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA. Electronic address: pthomp@usc.edu.
INVESTIGATORS
JOURNAL
VOLUME: 36 Suppl 1
ISSUE:
TITLE: Neurobiology of aging
ISOABBREVIATION: Neurobiol. Aging
YEAR: 2015
MONTH: Jan
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1558-1497
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Neurobiol Aging
COUNTRY: United States
ISSNLINKING: 0197-4580
NLMUNIQUEID: 8100437
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AG016570 NIA NIH HHS United States
EB01651 NIBIB NIH HHS United States
F30 AG041681 NIA NIH HHS United States
F30 AG041681 NIA NIH HHS United States
K01 AG030514 NIA NIH HHS United States
K01 AG030514 NIA NIH HHS United States
K99 MH102357 NIMH NIH HHS United States
LM05639 NLM NIH HHS United States
P30 AG010129 NIA NIH HHS United States
P30 AG010129 NIA NIH HHS United States
P41 EB015922 NIBIB NIH HHS United States
P50 AG016570 NIA NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 EB016516 NIBIB NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 LM005639 NLM NIH HHS United States
R21 EB001561 NIBIB NIH HHS United States
R21 RR019771 NCRR NIH HHS United States
RF1 AG041915 NIA NIH HHS United States
RR019771 NCRR NIH HHS United States
U01 AG024904 NIA NIH HHS United States
U01 AG024904 NIA NIH HHS United States
U24 AG021886 NIA NIH HHS United States
U54 EB020403 NIBIB NIH HHS United States
UL1 TR001108 NCATS NIH HHS United States
Canadian Institutes of Health Research Canada
GENERAL NOTE
KEYWORDS
KEYWORD
Epistasis
GWAS
GWIA
Genome-wide
Interaction
Sure independence screening
Tensor-based morphometry
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Aged, 80 and over
Alzheimer Disease pathology
Epistasis, Genetic pathology
Female pathology
Genome-Wide Association Study pathology
Humans pathology
Magnetic Resonance Imaging methods
Male methods
Neuroimaging methods
Polymorphism, Single Nucleotide genetics
Risk genetics
Temporal Lobe pathology
Twins pathology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS647295 NLM
PMC4332874 NLM
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