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Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

dc.contributor.authorMoreno-Grau, S.
dc.contributor.authorde Rojas, I.
dc.contributor.authorHernández, I.
dc.contributor.authorQuintela, I.
dc.contributor.authorMontrreal, L.
dc.contributor.authorAlegret, M.
dc.contributor.authorHernández-Olasagarre, B.
dc.contributor.authorMadrid, L.
dc.contributor.authorGonzález-Perez, A.
dc.contributor.authorMaroñas, O.
dc.contributor.authorRosende-Roca, M.
dc.contributor.authorMauleón, A.
dc.contributor.authorVargas, L.
dc.contributor.authorLafuente, A.
dc.contributor.authorAbdelnour, C.
dc.contributor.authorRodríguez-Gómez, O.
dc.contributor.authorGil, S.
dc.contributor.authorSantos-Santos, M. Á
dc.contributor.authorEspinosa, A.
dc.contributor.authorOrtega, G.
dc.contributor.authorSanabria, Á
dc.contributor.authorPérez-Cordón, A.
dc.contributor.authorCañabate, P.
dc.contributor.authorMoreno, M.
dc.contributor.authorPreckler, S.
dc.contributor.authorRuiz, S.
dc.contributor.authorAguilera, N.
dc.contributor.authorPineda, J. A.
dc.contributor.authorMacías, J.
dc.contributor.authorAlarcón-Martín, E.
dc.contributor.authorSotolongo-Grau, O.
dc.contributor.authorAbdelnour, C.
dc.contributor.authorAlarcon, E.
dc.contributor.authorBenaque, A.
dc.contributor.authorBoada, M.
dc.contributor.authorBuendia, M.
dc.contributor.authorCarracedo Álvarez, Ángel
dc.contributor.authorCorbatón, A.
dc.contributor.authorDiego, S.
dc.contributor.authorGailhajenet, A.
dc.contributor.authorGarcía González, P.
dc.contributor.authorGuitart, M.
dc.contributor.authorIbarria, M.
dc.contributor.authorMacias, J.
dc.contributor.authorMartín, E.
dc.contributor.authorMartínez, M. T.
dc.contributor.authorMarquié, M.
dc.contributor.authorMonté-Rubio, G.
dc.contributor.authorOrellana, A.
dc.contributor.authorPancho, A.
dc.contributor.authorPelejà, E.
dc.contributor.authorReal, L. M.
dc.contributor.authorRuiz, A.
dc.contributor.authorRuiz, S.
dc.contributor.authorSáez, M. E.
dc.contributor.authorSanabria, A.
dc.contributor.authorSerrano-Rios, M.
dc.contributor.authorTárraga, L.
dc.contributor.authorValero, S.
dc.contributor.authorAdarmes-Gómez, A. D.
dc.contributor.authorÁlvarez, I.
dc.contributor.authorÁlvarez, V.
dc.contributor.authorAmer-Ferrer, G.
dc.contributor.authorAntequera, M.
dc.contributor.authorAntúnez, C.
dc.contributor.authorBaquero, M.
dc.contributor.authorBernal, M.
dc.contributor.authorBlesa, R.
dc.contributor.authorBuiza-Rueda, D.
dc.contributor.authorBullido, M. J.
dc.contributor.authorBurguera, J. A.
dc.contributor.authorCalero, M.
dc.contributor.authorCarrillo, F.
dc.contributor.authorCarrión-Claro, M.
dc.contributor.authorCasajeros, M. J.
dc.contributor.authorClarimón, J.
dc.contributor.authorCruz-Gamero, J. M.
dc.contributor.authorde Pancorbo, M. M.
dc.contributor.authordel Ser, T.
dc.contributor.authorDiez-Fairen, M.
dc.contributor.authorFortea, J.
dc.contributor.authorFranco, E.
dc.contributor.authorFrank-García, A.
dc.contributor.authorGarcía-Alberca, J. M.
dc.contributor.authorGarcia Madrona, S.
dc.contributor.authorGarcia-Ribas, G.
dc.contributor.authorGómez-Garre, P.
dc.contributor.authorHevilla, S.
dc.contributor.authorJesús, S.
dc.contributor.authorEspinosa, L.
dc.contributor.authorLage, C.
dc.contributor.authorLegaz, A.
dc.contributor.authorLleó, A.
dc.contributor.authorLópez de Munáin, A.
dc.contributor.authorLópez-García, S.
dc.contributor.authorMacias, D.
dc.contributor.authorManzanares, S.
dc.contributor.authorMarín, M.
dc.contributor.authorMarín-Muñoz, J.
dc.contributor.authorMarín, T.
dc.contributor.authorMartín Montes, A.
dc.contributor.authorMartínez, B.
dc.contributor.authorMartínez, C.
dc.contributor.authorMartínez, V.
dc.contributor.authorMartínez-Lage Álvarez, P.
dc.contributor.authorMedina, M.
dc.contributor.authorMendioroz Iriarte, M.
dc.contributor.authorMenéndez-González, M.
dc.contributor.authorMir, P.
dc.contributor.authorMolinuevo, J. L.
dc.contributor.authorPastor, A. B.
dc.contributor.authorPástor, P.
dc.contributor.authorPérez Tur, J.
dc.contributor.authorPeriñán-Tocino, T.
dc.contributor.authorPiñol Ripoll, G.
dc.contributor.authorRábano, A.
dc.contributor.authorReal de Asúa, D.
dc.contributor.authorRodrigo, S.
dc.contributor.authorRodríguez-Rodríguez, E.
dc.contributor.authorRoyo, J. L.
dc.contributor.authorRuiz, A.
dc.contributor.authorSanchez del Valle Díaz, R.
dc.contributor.authorSánchez-Juan, P.
dc.contributor.authorSastre, I.
dc.contributor.authorVicente, M. P.
dc.contributor.authorVivancos, L.
dc.contributor.authorGarcía-Ribas, G.
dc.contributor.authorPiñol-Ripoll, G.
dc.contributor.authorMedina, M.
dc.contributor.authorÁvila, J.
dc.date.accessioned2022-01-27T10:43:16Z
dc.date.available2022-01-27T10:43:16Z
dc.date.issued2019
dc.identifier.issn15525260
dc.identifier.otherhttps://alz-journals.onlinelibrary.wiley.com/doi/pdfdirect/10.1016/j.jalz.2019.06.4950?download=truees
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pubmed/31473137es
dc.identifier.urihttp://hdl.handle.net/20.500.11940/15992
dc.description.abstractINTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.en
dc.language.isoenges
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshCerebral Amyloid Angiopathy*
dc.subject.meshAlzheimer Disease*
dc.subject.meshGenetic Loci*
dc.subject.meshDementia*
dc.subject.meshMiddle Aged*
dc.subject.meshHumans*
dc.subject.meshEndophenotypes*
dc.subject.meshGenome-Wide Association Study*
dc.subject.meshGenetic Predisposition to Disease*
dc.subject.meshAged*
dc.titleGenome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE projecten
dc.typeArtigoes
dc.identifier.doi10.1016/j.jalz.2019.06.4950
dc.identifier.pmid31473137
dc.identifier.sophos33037
dc.issue.number10es
dc.journal.titleAlzheimers Dementes
dc.organizationServizo Galego de Saúde::Dirección Xeral de Asistencia Sanitaria::Fundación Pública Galega de Medicina Xenómicaes
dc.page.initial1333es
dc.page.final1347es
dc.rights.accessRightsopenAccesses
dc.subject.decsendofenotipos*
dc.subject.decsanciano*
dc.subject.decsangiopatía amiloide cerebral*
dc.subject.decsenfermedad de Alzheimer*
dc.subject.decsmediana edad*
dc.subject.decshumanos*
dc.subject.decsestudio de asociación genómica completa*
dc.subject.decssitios genéticos*
dc.subject.decspredisposición genética a la enfermedad*
dc.subject.decsdemencia*
dc.subject.keywordFPGMXes
dc.typefidesArtículo Originales
dc.typesophosArtículo Originales
dc.volume.number15es


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Alzheimers Dement. 2019 Oct;15(10):1333-1347

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