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(2018)
GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.
Nat Commun, 9 (1).
p. 5141.
ISSN 2041-1723
https://doi.org/10.1038/s41467-018-07340-5
SGUL Authors: Whincup, Peter Hynes
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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.
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| Additional Information: | 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/. © The Author(s) 2018 | |||||||||||||||||||||||||||||||||
| Keywords: | MEGASTROKE Consortium, MD Multidisciplinary | |||||||||||||||||||||||||||||||||
| SGUL Research Institute / Research Centre: | Academic Structure > Population Health Research Institute (INPH) | |||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Nat Commun | |||||||||||||||||||||||||||||||||
| ISSN: | 2041-1723 | |||||||||||||||||||||||||||||||||
| Language: | eng | |||||||||||||||||||||||||||||||||
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| Publisher License: | Creative Commons: Attribution 4.0 | |||||||||||||||||||||||||||||||||
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| PubMed ID: | 30510157 | |||||||||||||||||||||||||||||||||
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| URI: | https://openaccess.sgul.ac.uk/id/eprint/110466 | |||||||||||||||||||||||||||||||||
| Publisher's version: | https://doi.org/10.1038/s41467-018-07340-5 |
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