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

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dc.contributor.author Chauhan, Ganesh
dc.contributor.author Jiménez-Conde, Jordi
dc.contributor.author Debette, Stéphanie
dc.date.accessioned 2019-09-09T07:55:22Z
dc.date.available 2019-09-09T07:55:22Z
dc.date.issued 2019
dc.identifier.citation Chauhan G, Adams HHH, Satizabal CL, Bis JC, Teumer A, Sargurupremraj M. et al. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting. Neurology. 2019 Jan 16. pii: 10.1212/WNL.0000000000006851. DOI: 10.1212/WNL.0000000000006851
dc.identifier.issn 0028-3878
dc.identifier.uri http://hdl.handle.net/10230/42255
dc.description Data de publicació electrónica: 16-01-2019
dc.description.abstract OBJECTIVE: 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Lippincott Williams & Wilkins
dc.rights © Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY) https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Estils de vida
dc.subject.other Genètica
dc.subject.other Malalties cerebrovasculars
dc.title Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1212/WNL.0000000000006851
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/643417
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/640643
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/666881
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/667375
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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