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

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Smith, Albert Vernon
dc.contributor.author Gudnason, Vilmundur
dc.contributor.author Grétarsdóttir, Sólveig
dc.contributor.author Thorleifsson, Gudmar
dc.contributor.author Thorsteinsdottir, Unnur
dc.contributor.author Stefansson, Kari
dc.date.accessioned 2020-03-05T15:27:48Z
dc.date.available 2020-03-05T15:27:48Z
dc.date.issued 2018-12
dc.identifier.citation Franceschini, 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/s41467-018-07340-5
dc.identifier.issn 2041-1723
dc.identifier.uri https://hdl.handle.net/20.500.11815/1582
dc.description Publisher's version (útgefin grein)
dc.description.abstract Carotid 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.
dc.description.sponsorship The 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.
dc.format.extent 5141
dc.language.iso en
dc.publisher Springer Science and Business Media LLC
dc.relation.ispartofseries Nature Communications;9(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Cardiovascular diseases
dc.subject Cardiovascular genetics
dc.subject Genome-wide association studies
dc.subject Quantitative trait loci
dc.subject Blóðrásarsjúkdómar
dc.subject Erfðafræði
dc.subject Erfðarannsóknir
dc.subject hjarta
dc.title GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
dc.type info:eu-repo/semantics/article
dcterms.license Open 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/.
dc.description.version Peer Reviewed
dc.identifier.journal Nature Communications
dc.identifier.doi 10.1038/s41467-018-07340-5
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.department Læknadeild (HÍ)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

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