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Cited by 39Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchBioinformatics and Genomic Networks

Systems biology approach to late‐onset Alzheimer's disease genome‐wide association study identifies novel candidate genes validated using brain expression data and Caenorhabditis elegans experiments

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Mukherjee, Shubhabrata, Russell, Joshua C., Carr, Daniel T., Burgess, Jeremy D., Allen, Mariet, Serie, Daniel J., Boehme, Kevin L., Kauwe, John S.K. +7 more·2017·Alzheimer's & Dementia
DOI 10.1016/j.jalz.2017.01.016PMC PMC5568992
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Abstract

Introduction: We sought to determine whether a systems biology approach may identify novel late‐onset Alzheimer's disease (LOAD) loci. Methods: We performed gene‐wide association analyses and integrated results with human protein‐protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions. Results: We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1 , and ATP5H were associated with Aβ toxicity, and NDUFS3, SLC25A11, ATP5H , and APP were differentially expressed in the temporal cortex. Discussion: Network analyses identified novel LOAD candidate genes. We demonstrated a functional role for four of these in a C. elegans model and found enrichment of differentially expressed genes in the temporal cortex.

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Authors
Mukherjee, S., Russell, J. C., Carr, D. T., Burgess, J. D., Allen, M., Serie, D. J., Boehme, K. L., Kauwe, J. S. K., Naj, A. C., Fardo, D. W., Dickson, D. W., Montine, T. J., Ertekin‐Taner, N., Kaeberlein, M. R., & Crane, P. K.
Affiliations
  • University of Washington (US)
  • Mayo Clinic in Florida (US)
  • Brigham Young University (US)
  • University of Pennsylvania (US)
  • University of Kentucky (US)
  • Department of Neuroscience Mayo Clinic Florida Jacksonville Florida USA
Corresponding author
Mukherjee, Shubhabrata
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2017-02-24
Volume
13
Issue
10
Pages
1133-1142
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1016/j.jalz.2017.01.016
PMC
PMC5568992
OpenAlex
W2590653656
Cited by
39
References
5
Citations by year
2026: 3 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 6 · 2020: 1 · 2019: 6 · 2018: 6 · 2017: 4
FWCI
3.31
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alzheimer s & Dementia (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • UKnowledge (University of Kentucky) (submittedVersion, cc-by-nc-nd)
Funders
  • Labex
  • Institut National de la Santé et de la Recherche Médicale
  • Alzheimer’s Research UK (503176)
  • National Institute on Aging (R01 AG033193, AG081220, U01 AG032984, U24 AG021886, U01 AG016976)
  • National Heart, Lung, and Blood Institute (R01 HL105756)
  • Alzheimer's Association (ADGC‐10‐196728)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
late-onset Alzheimer's disease, genome-wide association study
MeSH terms
Mitochondrial ADP, ATP Translocases, Alzheimer Disease, Animals, Antigens, Neoplasm, Disease Models, Animal, Female, Gene Expression Regulation, Humans, Male, NADH Dehydrogenase, Temporal Lobe, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Caenorhabditis elegans, Polymorphism, Single Nucleotide, Membrane Transport Proteins, Animals, Genetically Modified, RNA Interference, Systems Biology, Early Growth Response Protein 1, Genome-Wide Association Study, Protein Interaction Maps, Heparin-binding EGF-like Growth Factor

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