GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Almenn færsla
dc.contributorHáskóli Íslandsen_US
dc.contributorUniversity of Icelanden_US
dc.contributor.authorSmith, Albert Vernon
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorGrétarsdóttir, Sólveig
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorStefansson, Kari
dc.contributor.departmentFaculty of Medicine (UI)en_US
dc.contributor.departmentLæknadeild (HÍ)en_US
dc.contributor.schoolHeilbrigðisvísindasvið (HÍ)en_US
dc.contributor.schoolSchool of Health Sciences (UI)en_US
dc.date.accessioned2020-03-05T15:27:48Z
dc.date.available2020-03-05T15:27:48Z
dc.date.issued2018-12
dc.descriptionPublisher's version (útgefin grein)en_US
dc.description.abstractCarotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.en_US
dc.description.sponsorshipThe work was supported by the following grants: National Institute of Health grants: R21HL123677, R21-HL140385, DK104806-01A1, R01-MD012765-01A1 (NF), National Institutes of Health awards R01HG009120, R01HG006399, U01CA194393, T32NS048004 (CG), the American Heart Association Grant #17POST33350042 (PV), the British Heart Foundation (RG/13/5/30112) and the National Institute for Health Research University College London Hospitals Biomedical Research Centre (RCL and RPH), the British Heart Foundation FS/14/55/30806 (JCH), the German Federal Ministry of Education and Research (BMBF) in the context of the e:Med program (e:AtheroSysMed), the DFG as part of the CRC 1123 (B3), and the FP7/2007-2103 European Union project CVgenes@target (grant agreement number Health-F2-2013-601456). We thank Li-Ming Gan for assistance with the STARNET study and Jon White for assistance with UCLEB analyses. Additional acknowledgements are included in Supplementary Note 2.en_US
dc.description.versionPeer Revieweden_US
dc.format.extent5141en_US
dc.identifier.citationFranceschini, N., Giambartolomei, C., de Vries, P.S. et al. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. Nat Commun 9, 5141 (2018). https://doi.org/10.1038/s41467-018-07340-5en_US
dc.identifier.doi10.1038/s41467-018-07340-5
dc.identifier.issn2041-1723
dc.identifier.journalNature Communicationsen_US
dc.identifier.urihttps://hdl.handle.net/20.500.11815/1582
dc.language.isoenen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.ispartofseriesNature Communications;9(1)
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCardiovascular diseasesen_US
dc.subjectCardiovascular geneticsen_US
dc.subjectGenome-wide association studiesen_US
dc.subjectQuantitative trait locien_US
dc.subjectBlóðrásarsjúkdómaren_US
dc.subjectErfðafræðien_US
dc.subjectErfðarannsókniren_US
dc.subjecthjartaen_US
dc.titleGWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomesen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dcterms.licenseOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_US

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