GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
Author(s)
Type
Journal Article
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.
Date Issued
2018-12-03
Date Acceptance
2018-09-24
Citation
Nature Communications, 2018, 9 (1)
ISSN
2041-1723
Publisher
Nature Research (part of Springer Nature)
Journal / Book Title
Nature Communications
Volume
9
Issue
1
Copyright Statement
© 2018 The Author(s). This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30510157
PII: 10.1038/s41467-018-07340-5
Subjects
ADAMTS9 Protein
Amino Acid Oxidoreductases
Carotid Intima-Media Thickness
Coronary Disease
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Lod Score
Plaque, Atherosclerotic
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Risk Factors
Publication Status
Published
Coverage Spatial
England
Article Number
ARTN 5141