A genome-wide association meta-analysis of all-cause and vascular dementia

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dc.contributor.authorFongang, Bernard
dc.contributor.authorSargurupremraj, Muralidharan
dc.contributor.authorJian, Xueqiu
dc.contributor.authorMishra, Aniket
dc.contributor.authorDamotte, Vincent
dc.contributor.authorRojas, Itziar de
dc.contributor.authorSkrobot, Olivia
dc.contributor.authorBis, Joshua C.
dc.contributor.authorFan, Kang-Hsien
dc.contributor.authorJacobsen, Erin
dc.contributor.authorLi, Gloria Hoi-Yee
dc.contributor.authorYang, Jingyun
dc.contributor.authorAlessandra, Bizzarro
dc.contributor.authorAlessandra, Lauria
dc.contributor.authorHilal, Saima
dc.contributor.authorChong, Joyce Ruifen
dc.contributor.authorChai, Yuek Ling
dc.contributor.authorKnol, M.J.
dc.contributor.authorPina Concas, Maria
dc.contributor.authorGiorgia, Girotto
dc.contributor.authorRiaz, Moeen
dc.contributor.authorYu, Chenglong
dc.contributor.authorGuojonsson, Alexander
dc.contributor.authorLacaze, Paul
dc.contributor.authorNaj, Adam C.
dc.contributor.authorGireud-Goss, Monica
dc.contributor.authorWadop, Yannick N.
dc.contributor.authorSoumare, Aicha
dc.contributor.authorBouteloup, Vincent
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorBattista, Petronilla
dc.contributor.authorSantin, Aurora
dc.contributor.authorSpedicati, Beatrice
dc.contributor.authorSardone, Rodolfo
dc.contributor.authorLauner, Lenore
dc.contributor.authorBressler, Jan
dc.contributor.authorGottesman, Rebecca F.
dc.contributor.authorLe Grand, Quentin
dc.contributor.authorCaro, Ilana
dc.contributor.authorRoshchupkin, Gennady V.
dc.contributor.authorLeonard, Hampton L.
dc.contributor.authorYang, Chaojie
dc.contributor.authorBartz, Traci M.
dc.contributor.authorBordes, Constance
dc.contributor.authorRidker, Paul M.
dc.contributor.authorGeerlings, Mirjam I.
dc.contributor.authorGasca, Natalie C.
dc.contributor.authorManichaikul, Ani
dc.contributor.authorNalls, Mike A.
dc.contributor.authorRich, Stephen S.
dc.contributor.authorSchmidt, Carsten O.
dc.contributor.authorTrompet, Stella
dc.contributor.authorSetten, Jessica van
dc.contributor.authorVugt, Marion van
dc.contributor.authorGrabe, Hans J.
dc.contributor.authorJukema, J. Wouter
dc.contributor.authorRissanen, Ina L.
dc.contributor.authorWassertheil-Smoller, Sylvia
dc.contributor.authorIkram, M. Arfan
dc.contributor.authorSimonsick, Eleanor M.
dc.contributor.authorLongstreth, W.T.
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorSattar, Naveed
dc.contributor.authorStott, David J.
dc.contributor.authorShiroma, Eric J.
dc.contributor.authorSigurdsson, Sigurdur
dc.contributor.authorGhanbari, Mohsen
dc.contributor.authorSchminke, Ulf
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorAparicio, Hugo J.
dc.contributor.authorBeiser, Alexa S.
dc.contributor.authorRomero, José R.
dc.contributor.authorLioutas, Vasileios
dc.contributor.authorWang, Ruiqi
dc.contributor.authorSarnowski, Chloe
dc.contributor.authorTeumer, Alexander
dc.contributor.authorVölker, Uwe
dc.contributor.authorMosley, Thomas H.
dc.contributor.authorMarquié, Marta
dc.contributor.authorGarcía González, Pablo
dc.contributor.authorOlivé, Clàudia
dc.contributor.authorPuerta, Raquel
dc.contributor.authorCano, Amanda
dc.contributor.authorSotolongo Grau, Óscar
dc.contributor.authorValero, Sergi
dc.contributor.authorPytel, Vanesa Verónica
dc.contributor.authorRosende-Roca, Maitée
dc.contributor.authorAlegret, Montserrat
dc.contributor.authorTàrraga, Lluís
dc.contributor.authorBoada, Mercè
dc.contributor.authorCarracedo, Ángel
dc.contributor.authorFranco Macías, Emilio
dc.contributor.authorPiñol Ripoll, Gerard
dc.contributor.authorGarcía Ribas, Guillermo
dc.contributor.authorPérez Tur, Jordi
dc.contributor.authorRoyo, Jose Luís
dc.contributor.authorGarcía Alberca, Jose María
dc.contributor.authorReal, Luis Miguel
dc.contributor.authorSáez, María Eugenia
dc.contributor.authorBullido, María J.
dc.contributor.authorCalero, Miguel
dc.contributor.authorMedina, Miguel
dc.contributor.authorMir, Pablo
dc.contributor.authorSánchez Juan, Pascual
dc.contributor.authorPastor, Pau
dc.contributor.authorÁlvarez, Victoria
dc.contributor.authorGrenier-Boley, Benjamin
dc.contributor.authorKüçükali, Fahri
dc.contributor.authorVan der Lee, Sven
dc.contributor.authorPeters, Oliver
dc.contributor.authorSchneider, Anja
dc.contributor.authorDichgans, Martin
dc.contributor.authorRujescu, Dan
dc.contributor.authorDeckert, Jürgen
dc.contributor.authorDüzel, Emrah
dc.contributor.authorWiltfang, Jens
dc.contributor.authorWagner, Michael
dc.contributor.authorGrimmer, Timo
dc.contributor.authorScarmeas, Nikolaos
dc.contributor.authorMoreno, Fermín
dc.contributor.authorSánchez Valle, Raquel
dc.contributor.authorReal, Luis M.
dc.contributor.authorRodríguez Rodríguez, Eloy
dc.contributor.authorLópez de Munain Arregui, Adolfo
dc.contributor.authorMendonça, Alexandre de
dc.contributor.authorHort, Jakub
dc.contributor.authorGraff, Caroline
dc.contributor.authorPapenberg, Goran
dc.contributor.authorGiedraitis, Vilmantas
dc.contributor.authorNordestgaard, Børge G.
dc.contributor.authorSoininen, Hilkka
dc.contributor.authorKivipelto, Miia
dc.contributor.authorHaapasalo, Annakaisa
dc.contributor.authorNicolás, Gael
dc.contributor.authorPasquier, Florence
dc.contributor.authorHanon, Olivier
dc.contributor.authorGrünblatt, Edna
dc.contributor.authorGalimberti, Daniela
dc.contributor.authorArosio, Beatrice
dc.contributor.authorMecocci, Patrizia
dc.contributor.authorSquassina, Alessio
dc.contributor.authorTremolizzo, Lucio
dc.contributor.authorRainero, Innocenzo
dc.contributor.authorSeripa, Davide
dc.contributor.authorWilliams, Julie
dc.contributor.authorAmouyel, Philippe
dc.contributor.authorJessen, Frank
dc.contributor.authorMagda, Tsolaki
dc.contributor.authorFrikke-Schmidt, Ruth
dc.contributor.authorSleegers, Kristel
dc.contributor.authorEngelborghs, Sebastiaan
dc.contributor.authorVandenberghe, Rik
dc.contributor.authorIngelsson, Martin
dc.contributor.authorRossi, Giacomina
dc.contributor.authorHiltunen, Mikko
dc.contributor.authorSims, Rebecca
dc.contributor.authorGugała-Iwaniuk, Magdalena
dc.contributor.authorLai, Mitchell K. P.
dc.contributor.authorVenketasubramanian, N.
dc.contributor.authorTan, Boon-Yeow
dc.contributor.authorCefalù, Angelo Baldassare
dc.contributor.authorArmstrong, Nicola J.
dc.contributor.authorBaschi, Roberta
dc.contributor.authorBordet, Regis
dc.contributor.authorBordet, Anne-Marie
dc.contributor.authorBrodaty, Henry
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorD'Onofrio, Grazia
dc.contributor.authorEsiri, Margaret
dc.contributor.authorGelé, Patrick
dc.contributor.authorJuárez Cedillo, Teresa
dc.contributor.authorKalaria, Raj
dc.contributor.authorKarhunen, Pekka
dc.contributor.authorLaczo, Jan
dc.contributor.authorLerch, Ondrej
dc.contributor.authorMasullo, Carlo
dc.contributor.authorMather, Karen A.
dc.contributor.authorMatoska, Vaclav
dc.contributor.authorMelkas, Susanna
dc.contributor.authorMonastero, Roberto
dc.contributor.authorNumbers, Katya
dc.contributor.authorPanza, Francesco
dc.contributor.authorPolvikoski, Tuomo M.
dc.contributor.authorQuinn, Joe
dc.contributor.authorRongve, Arvid
dc.contributor.authorSachdev, Perminder S.
dc.contributor.authorScamosci, Michela
dc.contributor.authorThalamuthu, Anbupalam
dc.contributor.authorTybjærg-Hansen, Anne
dc.contributor.authorVyhnalek, Martin
dc.contributor.authorWestaway, Shawn K.
dc.contributor.authorMartinsen, Amy E.
dc.contributor.authorSkogholt, Anne Heidi
dc.contributor.authorWiller, Cristen J.
dc.contributor.authorStordal, Eystein
dc.contributor.authorBråthen, Geir
dc.contributor.authorNielsen, Jonas Bille
dc.contributor.authorFritsche, Lars G.
dc.contributor.authorThomas, Laurent F.
dc.contributor.authorPedersen, Linda M.
dc.contributor.authorGabrielsen, Maiken E.
dc.contributor.authorDrange, Ole Kristian
dc.contributor.authorSando, Sigrid Botne
dc.contributor.authorMeisingset, Tore Wergeland
dc.contributor.authorChene, Genevieve
dc.contributor.authorZhou, Wei
dc.contributor.authorTzourio, Christophe
dc.contributor.authorTin, Adrienne
dc.contributor.authorLópez, Óscar L.
dc.contributor.authorMary, Haan
dc.contributor.authorAiello, Allison E.
dc.contributor.authorBørte, Sigrid
dc.contributor.authorBosnes, Ingunn
dc.contributor.authorVan Duijn, Cornelia
dc.contributor.authorCheung, Ching-Lung
dc.contributor.authorBennett, David A.
dc.contributor.authorChen, Christopher
dc.contributor.authorKamboh, M. Ilyas
dc.contributor.authorSatizabal, Claudia
dc.contributor.authorIkram, M. Kamran
dc.contributor.authorAdams, Hieab
dc.contributor.authorQiong, Yang
dc.contributor.authorSchellenberg, Gerard D.
dc.contributor.authorSelbæk, Geir
dc.contributor.authorHveem, Kristian
dc.contributor.authorAndreassen, Ole A.
dc.contributor.authorRamírez, Alfredo
dc.contributor.authorDufouil, Carole
dc.contributor.authorVan der Flier, Wiesje
dc.contributor.authorZwart, John-Anker
dc.contributor.authorDebette, Stéphanie
dc.contributor.authorFornage, Myriam
dc.contributor.authorWinsvold, Bendik
dc.contributor.authorLambert, Jean-Charles
dc.contributor.authorRuiz, Agustín
dc.contributor.authorKehoe, Patrick G.
dc.contributor.authorWeinstein, Galit
dc.contributor.authorSeshadri, Sudha
dc.date.accessioned2025-02-28T07:49:07Z
dc.date.available2025-02-28T07:49:07Z
dc.date.issued2024-09
dc.date.updated2025-02-28T07:49:07Z
dc.description.abstractINTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors. RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). DISCUSSION: Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD. Highlights: We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease.en
dc.description.sponsorshipNational Heart, Lung, and Blood Institute, Grant/Award Numbers: R01HL105756, RC2HL102419; National Institute on Aging, Grant/Award Number: AG033193; UT Health San Antonio Center for Biomedical Neuroscience, Grant/Award Numbers:AG059421, AG054076, AG049607, AG033090, AG066524, P30 AG066546,5P30AG059305-03, RF1 AG061729A1, 5U01AG052409-04; NINDS, Grant/Award Numbers: NS017950, UF1NS125513, K01NS126489en
dc.identifier.citationFongang, B., Sargurupremraj, M., Jian, X., Mishra, A., Damotte, V., de Rojas, I., Skrobot, O., Bis, J. C., Fan, K.-H., Jacobsen, E., Li, G. H.-Y., Yang, J., Alessandra, B., Alessandra, L., Hilal, S., Chong, J. R., Chai, Y. L., Knol, Concas, M. P., et al. (2024). A genome-wide association meta-analysis of all-cause and vascular dementia. Alzheimer’s and Dementia, 20(9), 5973-5995. https://doi.org/10.1002/ALZ.14115
dc.identifier.doi10.1002/ALZ.14115
dc.identifier.eissn1552-5279
dc.identifier.issn1552-5260
dc.identifier.urihttp://hdl.handle.net/20.500.14454/2396
dc.language.isoeng
dc.publisherJohn Wiley and Sons Inc
dc.rights© 2024 The Author(s).
dc.subject.otherAll-cause dementia
dc.subject.otherAlzheimer's disease
dc.subject.otherCross-ancestry
dc.subject.otherGenome-wide association study (GWAS)
dc.subject.otherGWAS meta-analysis
dc.subject.otherVascular dementia
dc.titleA genome-wide association meta-analysis of all-cause and vascular dementiaen
dc.typejournal article
dcterms.accessRightsopen access
oaire.citation.endPage5995
oaire.citation.issue9
oaire.citation.startPage5973
oaire.citation.titleAlzheimer's and Dementia
oaire.citation.volume20
oaire.licenseConditionhttps://creativecommons.org/licenses/by/4.0/
oaire.versionCVoR
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