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Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

2019-01Journal article Open access
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dc.contributor.authorChauhan, Ganesh
dc.contributor.authorAdams, Hieab H.H.
dc.contributor.authorSatizabal, Claudia L.
dc.contributor.authorBis, Joshua C.
dc.contributor.authorTeumer, Alexander
dc.contributor.authorSargurupremraj, Muralidharan
dc.contributor.authorHofer, Edith
dc.contributor.authorTrompet, Stella
dc.contributor.authorHilal, Saima
dc.contributor.authorSmith, Albert Vernon
dc.contributor.authorJian, Xueqiu
dc.contributor.authorChen, Christopher
dc.contributor.authorCheng, Ching-Yu
dc.contributor.authorWong, Tien Y.
dc.contributor.authorIkram, Mohammad K.
dc.contributor.authorvan der Lee, Sven J.
dc.contributor.authorAmin, Najaf
dc.contributor.authorChouraki, Vincent
dc.contributor.authorDeStefano, Anita L.
dc.contributor.authorAparicio, Hugo J.
dc.contributor.authorRomero, Jose R.
dc.contributor.authorSharma, Pankaj
dc.contributor.authorMaillard, Pauline
dc.contributor.authorDeCarli, Charles
dc.contributor.authorWardlaw, Joanna M.
dc.contributor.authorHernández, Maria del C. Valdés
dc.contributor.authorLuciano, Michelle
dc.contributor.authorLiewald, David
dc.contributor.authorDeary, Ian J.
dc.contributor.authorStarr, John M.
dc.contributor.authorBastin, Mark E.
dc.contributor.authorMuñoz Maniega, Susana
dc.contributor.authorSudlow, Cathie L.M.
dc.contributor.authorSlagboom, P. Eline
dc.contributor.authorBeekman, Marian
dc.contributor.authorDeelen, Joris
dc.contributor.authorUh, Hae-Won
dc.contributor.authorLemmens, Robin
dc.contributor.authorBrodaty, Henry
dc.contributor.authorWright, Margaret J.
dc.contributor.authorAmes, David
dc.contributor.authorBoncoraglio, Giorgio B.
dc.contributor.authorHopewell, Jemma C.
dc.contributor.authorRosand, Jonathan
dc.contributor.authorBeecham, Ashley H.
dc.contributor.authorBlanton, Susan H.
dc.contributor.authorWright, Clinton B.
dc.contributor.authorSacco, Ralph L.
dc.contributor.authorWen, Wei
dc.contributor.authorThalamuthu, Anbupalam
dc.contributor.authorArmstrong, Nicola J.
dc.contributor.authorChong, Elizabeth
dc.contributor.authorSchofield, Peter R.
dc.contributor.authorKwok, John B.
dc.contributor.authorWoo, Daniel
dc.contributor.authorvan der Grond, Jeroen
dc.contributor.authorStott, David J.
dc.contributor.authorFord, Ian
dc.contributor.authorJukema, J. Wouter
dc.contributor.authorVernooij, Meike W.
dc.contributor.authorHofman, Albert
dc.contributor.authorUitterlinden, André G.
dc.contributor.authorvan der Lugt, Aad
dc.contributor.authorWittfeld, Katharina
dc.contributor.authorGrabe, Hans J.
dc.contributor.authorCole, John W.
dc.contributor.authorHosten, Norbert
dc.contributor.authorvon Sarnowski, Bettina
dc.contributor.authorVölker, Uwe
dc.contributor.authorLevi, Christopher
dc.contributor.authorJimenez-Conde, Jordi
dc.contributor.authorMeschia, James F.
dc.contributor.authorSlowik, Agnieszka
dc.contributor.authorThijs, Vincent
dc.contributor.authorLindgren, Arne
dc.contributor.authorMelander, Olle
dc.contributor.authorMalik, Rainer
dc.contributor.authorGrewal, Raji P.
dc.contributor.authorRundek, Tatjana
dc.contributor.authorRexrode, Kathy
dc.contributor.authorRothwell, Peter M.
dc.contributor.authorArnett, Donna K.
dc.contributor.authorJern, Christina
dc.contributor.authorJohnson, Julie A.
dc.contributor.authorBenavente, Oscar R.
dc.contributor.authorWasssertheil-Smoller, Sylvia
dc.contributor.authorLee, Jin-Moo
dc.contributor.authorTraylor, Matthew
dc.contributor.authorWong, Quenna
dc.contributor.authorMitchell, Braxton D.
dc.contributor.authorRich, Stephen S.
dc.contributor.authorMcArdle, Patrick F.
dc.contributor.authorGeerlings, Mirjam I.
dc.contributor.authorvan der Graaf, Yolanda
dc.contributor.authorde Bakker, Paul I.W.
dc.contributor.authorAsselbergs, Folkert W.
dc.contributor.authorSrikanth, Velandai
dc.contributor.authorThomson, Russell
dc.contributor.authorPulit, Sara L.
dc.contributor.authorMcWhirter, Rebekah
dc.contributor.authorMoran, Chris
dc.contributor.authorCallisaya, Michele
dc.contributor.authorPhan, Thanh
dc.contributor.authorRutten-Jacobs, Loes C.A.
dc.contributor.authorBevan, Steve
dc.contributor.authorTzourio, Christophe
dc.contributor.authorMather, Karen A.
dc.contributor.authorSachdev, Perminder S.
dc.contributor.authorvan Duijn, Cornelia M.
dc.contributor.authorAmouyel, Philippe
dc.contributor.authorWorrall, Bradford B.
dc.contributor.authorDichgans, Martin
dc.contributor.authorKittner, Steven J.
dc.contributor.authorMarkus, Hugh S.
dc.contributor.authorIkram, Mohammad A.
dc.contributor.authorFornage, Myriam
dc.contributor.authorLauner, Lenore J.
dc.contributor.authorSeshadri, Sudha
dc.contributor.authorLongstreth, W.T.
dc.contributor.authorDebette, Stéphanie
dc.contributor.authorMazoyer, Bernard
dc.contributor.authorStroke Genetics Network
dc.contributor.authorInternational Stroke Genetics Consortium
dc.contributor.authorMETASTROKE
dc.contributor.authorAlzheimer’s Disease Genetics Consortium
dc.contributor.authorNeurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
dc.contributor.authorZhu, Yi-Cheng
dc.contributor.authorKaffashian, Sara
dc.contributor.authorSchilling, Sabrina
dc.contributor.authorBeecham, Gary W.
dc.contributor.authorMontine, Thomas J.
dc.contributor.authorSchellenberg, Gerard D.
dc.contributor.authorKjartansson, Olafur
dc.contributor.authorGuðnason, Vilmundur
dc.contributor.authorKnopman, David S.
dc.contributor.authorGriswold, Michael E.
dc.contributor.authorWindham, B. Gwen
dc.contributor.authorGottesman, Rebecca F.
dc.contributor.authorMosley, Thomas H.
dc.contributor.authorSchmidt, Reinhold
dc.contributor.authorSaba, Yasaman
dc.contributor.authorSchmidt, Helena
dc.contributor.authorTakeuchi, Fumihiko
dc.contributor.authorYamaguchi, Shuhei
dc.contributor.authorNabika, Toru
dc.contributor.authorKato, Norihiro
dc.contributor.authorRajan, Kumar B.
dc.contributor.authorAggarwal, Neelum T.
dc.contributor.authorDe Jager, Philip L.
dc.contributor.authorEvans, Denis A.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorRice, Kenneth
dc.contributor.authorLopez, Oscar L.
dc.contributor.authorLiao, Jiemin
dc.date.accessioned2020-04-24T10:58:54Z
dc.date.available2020-04-24T10:58:54Z
dc.date.issued2019-01
dc.descriptionCollaborators (845): Astrid M. Vicentept_PT
dc.descriptionFree PMC article:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369905/pt_PT
dc.description.abstractObjective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNeurology. 2019 Jan 16. pii: 10.1212/WNL.0000000000006851. doi: 10.1212/WNL.0000000000006851. [Epub ahead of print]pt_PT
dc.identifier.doi10.1212/WNL.0000000000006851pt_PT
dc.identifier.issn1526-632X
dc.identifier.urihttp://hdl.handle.net/10400.18/6509
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWolters Kluwer Health/ American Academy of Neurologypt_PT
dc.relation.publisherversionhttps://n.neurology.org/content/92/5/e486.longpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectGenome-wide Associationpt_PT
dc.subjectMatter Hyperintensity Volumept_PT
dc.subjectSmall Vessel Diseasept_PT
dc.subjectMendelian Randomizationpt_PT
dc.subjectIschemic Strokept_PT
dc.subjectBlood Pressurept_PT
dc.subjectSilentpt_PT
dc.subjectMeta-analysispt_PT
dc.subjectPolymorphismspt_PT
dc.subjectInsightspt_PT
dc.subjectDoenças Cardio e Cérebro-vascularespt_PT
dc.titleGenetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based settingpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage503pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage486pt_PT
oaire.citation.titleNeurologypt_PT
oaire.citation.volume92pt_PT
rcaap.embargofctDe acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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