Convergent genetic and expression data implicate immunity in Alzheimer's disease

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dc.contributor.authorJones, Lesley
dc.contributor.authorLambert, Jean-Charles
dc.contributor.authorWang, Li-San
dc.contributor.authorChoi, Seung-Hoan
dc.contributor.authorHarold, Denise
dc.contributor.authorVedernikov, Alexey
dc.contributor.authorEscott-Price, Valentina
dc.contributor.authorStone, Timothy
dc.contributor.authorRichards, Alexander
dc.contributor.authorBellenguez, Céline
dc.contributor.authorIbrahim-Verbaas, Carla A.
dc.contributor.authorNaj, Adam C.
dc.contributor.authorSims, Rebecca
dc.contributor.authorGerrish, Amy
dc.contributor.authorJun, Gyungah
dc.contributor.authorDeStefano, Anita L.
dc.contributor.authorBis, Joshua C.
dc.contributor.authorBeecham, Gary W.
dc.contributor.authorGrenier-Boley, Benjamin
dc.contributor.authorRusso, Giancarlo
dc.contributor.authorThornton-Wells, Tricia A.
dc.contributor.authorJones, Nicola
dc.contributor.authorSmith, Albert V.
dc.contributor.authorChouraki, Vincent
dc.contributor.authorThomas, Charlene
dc.contributor.authorIkram, M. Arfan
dc.contributor.authorZelenika, Diana
dc.contributor.authorVardarajan, Badri N.
dc.contributor.authorKamatani, Yoichiro
dc.contributor.authorLin, Chiao-Feng
dc.contributor.authorSchmidt, Helena
dc.contributor.authorKunkle, Brian
dc.contributor.authorDunstan, Melanie L.
dc.contributor.authorRuiz, Agustin
dc.contributor.authorBihoreau, Marie-Thérèse
dc.contributor.authorReitz, Christiane
dc.contributor.authorPasquier, Florence
dc.contributor.authorHollingworth, Paul
dc.contributor.authorHanon, Olivier
dc.contributor.authorFitzpatrick, Annette L.
dc.contributor.authorBuxbaum, Joseph D.
dc.contributor.authorCampion, Dominique
dc.contributor.authorCrane, Paul K.
dc.contributor.authorBecker, Tim
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorCruchaga, Carlos
dc.contributor.authorCraig, David
dc.contributor.authorAmin, Najaf
dc.contributor.authorBerr, Claudine
dc.contributor.authorLopez, Oscar L.
dc.contributor.authorDe Jager, Philip L.
dc.contributor.authorDeramecourt, Vincent
dc.contributor.authorJohnston, Janet A.
dc.contributor.authorEvans, Denis
dc.contributor.authorLovestone, Simon
dc.contributor.authorLetteneur, Luc
dc.contributor.authorKornhuber, Johanes
dc.contributor.authorTárraga, Lluís
dc.contributor.authorRubinsztein, David C.
dc.contributor.authorEiriksdottir, Gudny
dc.contributor.authorSleegers, Kristel
dc.contributor.authorGoate, Alison M.
dc.contributor.authorFiévet, Nathalie
dc.contributor.authorHuentelman, Matthew J.
dc.contributor.authorGill, Michael
dc.contributor.authorEmilsson, Valur
dc.contributor.authorBrown, Kristelle
dc.contributor.authorKamboh, M. Ilyas
dc.contributor.authorKeller, Lina
dc.contributor.authorBarberger-Gateau, Pascale
dc.contributor.authorMcGuinness, Bernadette
dc.contributor.authorLarson, Eric B.
dc.contributor.authorMyers, Amanda J.
dc.contributor.authorDufouil, Carole
dc.contributor.authorTodd, Stephen
dc.contributor.authorWallon, David
dc.contributor.authorLove, Seth
dc.contributor.authorKehoe, Pat
dc.contributor.authorRogaeva, Ekaterina
dc.contributor.authorGallacher, John
dc.contributor.authorGeorge-Hyslop, Peter St
dc.contributor.authorClarimon, Jordi
dc.contributor.authorLleὀ, Alberti
dc.contributor.authorBayer, Anthony
dc.contributor.authorTsuang, Debby W.
dc.contributor.authorYu, Lei
dc.contributor.authorTsolaki, Magda
dc.contributor.authorBossù, Paola
dc.contributor.authorSpalletta, Gianfranco
dc.contributor.authorProitsi, Petra
dc.contributor.authorCollinge, John
dc.contributor.authorSorbi, Sandro
dc.contributor.authorGarcia, Florentino Sanchez
dc.contributor.authorFox, Nick
dc.contributor.authorHardy, John
dc.contributor.authorNaranjo, Maria Candida Deniz
dc.contributor.authorRazquin, Cristina
dc.contributor.authorBosco, Paola
dc.contributor.authorClarke, Robert
dc.contributor.authorBrayne, Carol
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorMancuso, Michelangelo
dc.contributor.authorMoebus, Susanne
dc.contributor.authorMecocci, Patrizia
dc.contributor.authordel Zompo, Maria
dc.contributor.authorMaier, Wolfgang
dc.contributor.authorHampel, Harald
dc.contributor.authorPilotto, Alberto
dc.contributor.authorBullido, Maria
dc.contributor.authorPanza, Francesco
dc.contributor.authorCaffarra, Paolo
dc.contributor.authorNacmias, Benedetta
dc.contributor.authorGilbert, John R.
dc.contributor.authorMayhaus, Manuel
dc.contributor.authorJessen, Frank
dc.contributor.authorDichgans, Martin
dc.contributor.authorLannfelt, Lars
dc.contributor.authorHakonarson, Hakon
dc.contributor.authorPichler, Sabrina
dc.contributor.authorCarrasquillo, Minerva M.
dc.contributor.authorIngelsson, Martin
dc.contributor.authorBeekly, Duane
dc.contributor.authorAlavarez, Victoria
dc.contributor.authorZou, Fanggeng
dc.contributor.authorValladares, Otto
dc.contributor.authorYounkin, Steven G.
dc.contributor.authorCoto, Eliecer
dc.contributor.authorHamilton-Nelson, Kara L.
dc.contributor.authorMateo, Ignacio
dc.contributor.authorOwen, Michael J.
dc.contributor.authorFaber, Kelley M.
dc.contributor.authorJonsson, Palmi V.
dc.contributor.authorCombarros, Onofre
dc.contributor.authorO'Donovan, Michael C.
dc.contributor.authorCantwell, Laura B.
dc.contributor.authorSoininen, Hilkka
dc.contributor.authorBlacker, Deborah
dc.contributor.authorMead, Simon
dc.contributor.authorMosley, Thomas H.
dc.contributor.authorBennett, David A.
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorFratiglioni, Laura
dc.contributor.authorHolmes, Clive
dc.contributor.authorde Bruijn, Renee FAG
dc.contributor.authorPassmore, Peter
dc.contributor.authorMontine, Thomas J.
dc.contributor.authorBettens, Karolien
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorBrice, Alexis
dc.contributor.authorMorgan, Kevin
dc.contributor.authorForoud, Tatiana M.
dc.contributor.authorKukull, Walter A.
dc.contributor.authorHannequin, Didier
dc.contributor.authorPowell, John F.
dc.contributor.authorNalls, Michael A.
dc.contributor.authorRitchie, Karen
dc.contributor.authorLunetta, Kathryn L.
dc.contributor.authorKauwe, John SK
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorRiemenschneider, Matthias
dc.contributor.authorBoada, Mercè
dc.contributor.authorHiltunen, Mikko
dc.contributor.authorMartin, Eden R.
dc.contributor.authorPastor, Pau
dc.contributor.authorSchmidt, Reinhold
dc.contributor.authorRujescu, Dan
dc.contributor.authorDartigues, Jean-François
dc.contributor.authorMayeux, Richard
dc.contributor.authorTzourio, Christophe
dc.contributor.authorHofman, Albert
dc.contributor.authorNöthen, Markus M.
dc.contributor.authorGraff, Caroline
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorHaines, Jonathan L.
dc.contributor.authorLathrop, Mark
dc.contributor.authorPericak-Vance, Margaret A.
dc.contributor.authorLauner, Lenore J.
dc.contributor.authorFarrer, Lindsay A.
dc.contributor.authorvan Duijn, Cornelia M.
dc.contributor.authorVan Broekhoven, Christine
dc.contributor.authorRamirez, Alfredo
dc.contributor.authorSchellenberg, Gerard D.
dc.contributor.authorSeshadri, Sudha
dc.contributor.authorAmouyel, Philippe
dc.contributor.authorWilliams, Julie
dc.contributor.authorHolmans, Peter A.
dc.contributor.departmentDepartment of Medical & Molecular Genetics, IU School of Medicineen_US
dc.date.accessioned2017-04-12T19:33:51Z
dc.date.available2017-04-12T19:33:51Z
dc.date.issued2015-06
dc.description.abstractBackground 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. 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. Results 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 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationJones, L., Lambert, J.-C., Wang, L.-S., Choi, S.-H., Harold, D., Vedernikov, A., … Holmans, P. A. (2015). Convergent genetic and expression data implicate immunity in Alzheimer’s disease. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association, 11(6), 658–671. http://doi.org/10.1016/j.jalz.2014.05.1757en_US
dc.identifier.issn1552-5260en_US
dc.identifier.urihttps://hdl.handle.net/1805/12249
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.jalz.2014.05.1757en_US
dc.relation.journalAlzheimer's & dementia : the journal of the Alzheimer's Associationen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectAlzheimer Diseaseen_US
dc.subjectgeneticsen_US
dc.subjectmetabolismen_US
dc.subjectBrainen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.titleConvergent genetic and expression data implicate immunity in Alzheimer's diseaseen_US
dc.typeArticleen_US
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