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

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


Title: GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
Author: Smith, Albert Vernon   orcid.org/0000-0003-1942-5845
Gudnason, Vilmundur   orcid.org/0000-0001-5696-0084
Grétarsdóttir, Sólveig
Thorleifsson, Gudmar   orcid.org/0000-0003-4623-9087
Thorsteinsdottir, Unnur   orcid.org/0000-0002-7049-2827
Stefansson, Kari   orcid.org/0000-0003-1676-864X
Date: 2018-12
Language: English
Scope: 5141
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Faculty of Medicine (UI)
Læknadeild (HÍ)
Series: Nature Communications;9(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-018-07340-5
Subject: Cardiovascular diseases; Cardiovascular genetics; Genome-wide association studies; Quantitative trait loci; Blóðrásarsjúkdómar; Erfðafræði; Erfðarannsóknir; hjarta
URI: https://hdl.handle.net/20.500.11815/1582

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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

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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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/.

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