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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.

Original publication

DOI

10.1038/s41467-018-07340-5

Type

Journal article

Journal

Nature communications

Publication Date

03/12/2018

Volume

9

Addresses

Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27516, USA.

Keywords

MEGASTROKE Consortium, Humans, Coronary Disease, Genetic Predisposition to Disease, Amino Acid Oxidoreductases, Risk Factors, Lod Score, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Plaque, Atherosclerotic, Carotid Intima-Media Thickness, ADAMTS9 Protein