You are here
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.
Wednesday,2020-11-18 16:45 America/Los_Angeles — ecterry
| Title | 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. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Mukherjee, S, Russell, JC, Carr, DT, Burgess, JD, Allen, M, Serie, DJ, Boehme, KL, Kauwe, JSK, Naj, AC, Fardo, DW, Dickson, DW, Montine, TJ, Ertekin-Taner, N, Kaeberlein, MR, Crane, PK |
| Journal | Alzheimers Dement |
| Volume | 13 |
| Issue | 10 |
| Pagination | 1133-1142 |
| Date Published | 2017 Oct |
| ISSN | 1552-5279 |
| Keywords | Alzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Animals, Genetically Modified, Antigens, Neoplasm, Caenorhabditis elegans, Disease Models, Animal, Early Growth Response Protein 1, Female, Gene Expression Regulation, Genome-Wide Association Study, Heparin-binding EGF-like Growth Factor, Humans, Male, Membrane Transport Proteins, Mitochondrial ADP, ATP Translocases, NADH Dehydrogenase, Polymorphism, Single Nucleotide, Protein Interaction Maps, RNA Interference, Systems Biology, Temporal Lobe |
| Abstract | <p><b>INTRODUCTION: </b>We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>DISCUSSION: </b>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.</p> |
| DOI | 10.1016/j.jalz.2017.01.016 |
| Alternate Journal | Alzheimers Dement |
| PubMed ID | 28242297 |
| PubMed Central ID | PMC5568992 |
| Grant List | U01 HG006375 / HG / NHGRI NIH HHS / United States K25 AG043546 / AG / NIA NIH HHS / United States N01AG12100 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States P50 AG016574 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States RF1 AG051504 / AG / NIA NIH HHS / United States R01 AG042437 / AG / NIA NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01 AG032990 / AG / NIA NIH HHS / United States R01 NS080820 / NS / NINDS NIH HHS / United States U01 AG006781 / AG / NIA NIH HHS / United States R01 AG038518 / AG / NIA NIH HHS / United States U01 AG046139 / AG / NIA NIH HHS / United States / / Wellcome Trust / United Kingdom P30 AG013280 / AG / NIA NIH HHS / United States |
ePub date:
17/10