Convergent genetic and expression data implicate immunity in Alzheimer's disease
Data(s) |
01/06/2015
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Resumo |
<p>Background: 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>Methods: 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>Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).</p><p>Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. (C) 2015 Published by Elsevier Inc. on behalf of The Alzheimer's Association.</p> |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Jones , L , Lambert , J-C , Wang , L-S , Choi , S-H , Harold , D , Vedernikov , A , Escott-Price , V , Stone , T , Richards , A , Ibrahim-Verbaas , C A , Naj , A C , Sims , R , Gerrish , A , Craig , D , Johnston , J A , McGuinness , B , Todd , S & Passmore , P 2015 , ' Convergent genetic and expression data implicate immunity in Alzheimer's disease ' Alzheimers & dementia , vol 11 , no. 6 , pp. 658-671 . DOI: 10.1016/j.jalz.2014.05.1757 |
Palavras-Chave | #Alzheimer's disease #Dementia #Neurodegeneration #Immune response #Endocytosis #Cholesterol metabolism #Ubiquitination #Pathway analysis #ALIGATOR #Weighted gene co-expression network analysis #GENOME-WIDE ASSOCIATION #NETWORK ANALYSIS #UNITED-STATES #PREVALENCE #VARIANTS #POPULATION #BRAIN #LISTS |
Tipo |
article |