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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.
Item Type: | Journal Article |
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Publication: | NATURE COMMUNICATIONS |
Publisher: | NATURE PUBLISHING GROUP |
Additional Information: | Copyright of this article belongs to NATURE PUBLISHING GROUP |
Department/Centre: | Autonomous Societies / Centres > Centre for Brain Research |
Date Deposited: | 01 Jan 2019 17:35 |
Last Modified: | 27 Feb 2019 09:06 |
URI: | http://eprints.iisc.ac.in/id/eprint/61286 |
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