Evidence map›Paper›PMID 25264344›Full record

ArticleNeurobiology of aging2015

Genome-wide interaction analysis reveals replicated epistatic effects on brain structure.

Derrek P Hibar, Jason L Stein, Neda Jahanshad, Omid Kohannim, Xue Hua, Arthur W Toga, Katie L McMahon, Greig I de Zubicaray, Nicholas G Martin, Margaret J Wright and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Unravelling the genetic architecture of cerebral small vessel disease in the context of stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Brain Imaging Genomics: Integrated Analysis and Machine Learning.Proceedings of the IEEE. Institute of Electrical and Electronics Engineers · 2020
    Article
  8. Quantitative Trait Module-Based Genetic Analysis of Alzheimer's Disease.International journal of molecular sciences · 2019
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Combinations of Genetic Variants Occurring Exclusively in Patients.Computational and structural biotechnology journal · 2017
    Review
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Derrek P HibarImaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Jason L SteinImaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Neda JahanshadImaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Omid KohannimImaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Xue HuaImaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Arthur W TogaImaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
Katie L McMahonCentre for Magnetic Resonance, School of Psychology, University of Queensland, Brisbane, Queensland, Australia.
Greig I de ZubicarayFunctional Magnetic Resonance Imaging Laboratory, School of Psychology, University of Queensland, Brisbane, Queensland, Australia.
Nicholas G MartinGenetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
Margaret J WrightGenetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
Alzheimer's Disease Neuroimaging Initiative
Michael W WeinerDepartment 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.
Paul M ThompsonImaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA. Electronic address: pthomp@usc.edu.
University of Southern California · USQIMR Berghofer Medical Research Institute · AUUniversity of Queensland · AUUniversity of California, San Francisco · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI DECARLI, CHARLES · 1991 to 2020
$28.3M
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
UCLA ALZHEIMERS DISEASE RESEARCH CENTERP50AG016570 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BREDESEN, DALE E. · 1999 to 2014
$25.9M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
TR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VAN HORN, JOHN DARRELL · 2012 to 2022
$14.1M
Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1M
Growth factors, neuroinflammation, exercise, and brain integrityRF1AG041915 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2014
$2.9M
HARDI Mapping of Disease Effects on the BrainR01EB008432 · NIBIB · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI THOMPSON, PAUL M · 2009 to 2012
$2.6M
Genetic influences on the brain: A twin imaging studyR01HD050735 · NICHD · QUEENSLAND INSTITUTE OF MEDICAL RESEARCH · PI WRIGHT, MARGARET JANE · 2007 to 2011
$2.6M
Alzheimer's disease risk analyzed using population imaging genomicsR01AG040060 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2011 to 2016
$2.5M
CIHRNCATS NIH HHS UL1 TR001108NCRR NIH HHS R21 RR019771NCRR NIH HHS RR019771NIA NIH HHS AG016570NIA NIH HHS F30 AG041681NIA NIH HHS K01 AG030514NIA NIH HHS P30 AG010129NIA NIH HHS P50 AG016570NIA NIH HHS R01 AG040060NIA NIH HHS RF1 AG041915NIA NIH HHS U01 AG024904NIA NIH HHS U24 AG021886NIBIB NIH HHS EB01651NIBIB NIH HHS P41 EB015922NIBIB NIH HHS R01 EB007813NIBIB NIH HHS R01 EB008281NIBIB NIH HHS R01 EB008432NIBIB NIH HHS R01 EB016516NIBIB NIH HHS R21 EB001561NIBIB NIH HHS U54 EB020403NICHD NIH HHS R01 HD050735NIMH NIH HHS K99 MH102357NLM NIH HHS LM05639NLM NIH HHS R01 LM005639
6 · The paper itself

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.

Indexed as

Epistasis, GeneticGenome-Wide Association StudyAgedAged, 80 and overAlzheimer DiseaseFemaleHumansMagnetic Resonance ImagingMaleNeuroimagingPolymorphism, Single NucleotideRiskTemporal LobeTwinsEpistasisGenome-wideGWASGWIAInteractionSure independence screeningTensor-based morphometry

Identifiers

PMID25264344
PMCPMC4332874
OpenAlexW2138322459

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.