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Convergent genetic and expression data implicate immunity in Alzheimer's disease.
Wednesday,2016-04-13 11:24 America/Los_Angeles — zdrager
| Title | Convergent genetic and expression data implicate immunity in Alzheimer's disease. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Corporate/Institutional Authors | International Genomics of Alzheimer's Disease Consortium (IGAP) |
| Journal | Alzheimers Dement |
| Volume | 11 |
| Issue | 6 |
| Pagination | 658-71 |
| Date Published | 2015 Jun |
| ISSN | 1552-5279 |
| Keywords | Algorithms, Alzheimer Disease, Brain, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide |
| Abstract | <p><b>BACKGROUND: </b>Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.</p><p><b>METHODS: </b>The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.</p><p><b>RESULTS: </b>ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10(-11)), cholesterol transport (P = 2.96 × 10(-9)), and proteasome-ubiquitin activity (P = 1.34 × 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).</p><p><b>CONCLUSIONS: </b>The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.</p> |
| DOI | 10.1016/j.jalz.2014.05.1757 |
| Alternate Journal | Alzheimers Dement |
| PubMed ID | 25533204 |
| PubMed Central ID | PMC4672734 |
| Grant List | 081864 / / Wellcome Trust / United Kingdom 089703 / / Wellcome Trust / United Kingdom 095317 / / Wellcome Trust / United Kingdom 100140 / / Wellcome Trust / United Kingdom 167 / / Alzheimer's Society / United Kingdom HHSN268201200036C / HL / NHLBI NIH HHS / United States MC_U123192748 / / Medical Research Council / United Kingdom N01 AG012100 / AG / NIA NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N01 HC055015 / HC / NHLBI NIH HHS / United States N01 HC055016 / HC / NHLBI NIH HHS / United States N01 HC055018 / HC / NHLBI NIH HHS / United States N01 HC055019 / HC / NHLBI NIH HHS / United States N01 HC055020 / HC / NHLBI NIH HHS / United States N01 HC055021 / HC / NHLBI NIH HHS / United States N01 HC055022 / HC / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States P01 AG002219 / AG / NIA NIH HHS / United States P01 AG003991 / AG / NIA NIH HHS / United States P01 AG019724 / AG / NIA NIH HHS / United States P30 AG008017 / AG / NIA NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States P30 AG010124 / AG / NIA NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States P30 AG010133 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States P30 AG013854 / AG / NIA NIH HHS / United States P30 AG019610 / AG / NIA NIH HHS / United States P30 AG028377 / AG / NIA NIH HHS / United States P30 AG028383 / AG / NIA NIH HHS / United States P50 AG005128 / AG / NIA NIH HHS / United States P50 AG005131 / AG / NIA NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States P50 AG005134 / AG / NIA NIH HHS / United States P50 AG005138 / AG / NIA NIH HHS / United States P50 AG005146 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States P50 AG008671 / AG / NIA NIH HHS / United States P50 AG008702 / AG / NIA NIH HHS / United States P50 AG016570 / AG / NIA NIH HHS / United States P50 AG016573 / AG / NIA NIH HHS / United States P50 AG016574 / AG / NIA NIH HHS / United States P50 AG016582 / AG / NIA NIH HHS / United States P50 AG023501 / AG / NIA NIH HHS / United States P50 AG025688 / AG / NIA NIH HHS / United States R01 AG016495 / AG / NIA NIH HHS / United States R01 AG017173 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States R01 AG019085 / AG / NIA NIH HHS / United States R01 AG020688 / AG / NIA NIH HHS / United States R01 AG025259 / AG / NIA NIH HHS / United States R01 AG026916 / AG / NIA NIH HHS / United States R01 AG027944 / AG / NIA NIH HHS / United States R01 AG030146 / AG / NIA NIH HHS / United States R01 AG030653 / AG / NIA NIH HHS / United States R01 AG031581 / AG / NIA NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01 AG041718 / AG / NIA NIH HHS / United States R01 AG041797 / AG / NIA NIH HHS / United States R01 CA129769 / CA / NCI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R01 HL093029 / HL / NHLBI NIH HHS / United States R01 MH080295 / MH / NIMH NIH HHS / United States R01 NS059873 / NS / NINDS NIH HHS / United States R37 AG015473 / AG / NIA NIH HHS / United States RC2 AG036528 / AG / NIA NIH HHS / United States RC2 HL102419 / HL / NHLBI NIH HHS / United States U01 AG006781 / AG / NIA NIH HHS / United States U01 AG010483 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 AG049505 / AG / NIA NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States U01 HG004610 / HG / NHGRI NIH HHS / United States U01 HL096917 / HL / NHLBI NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U24 AG026395 / AG / NIA NIH HHS / United States UC2 HL103010 / HL / NHLBI NIH HHS / United States UL1 RR029893 / RR / NCRR NIH HHS / United States UL1 TR001108 / TR / NCATS NIH HHS / United States UL1 TR001445 / TR / NCATS NIH HHS / United States / / Medical Research Council / United Kingdom / / Wellcome Trust / United Kingdom |