A GWAS meta-analysis identified eight novel susceptibility loci for carotid intima-media thickness and one novel locus for carotid plaque, demonstrating significant genetic correlations with coronary heart disease and stroke.
Meta-Analysis (n=71,128)
Yes
What are the genetic susceptibility loci for carotid intima-media thickness and carotid plaque, and how do they correlate with cardiovascular outcomes?
This study identifies novel genetic loci associated with subclinical atherosclerosis measures (cIMT and plaque) and demonstrates their genetic correlation with clinical cardiovascular outcomes like CHD and stroke.
p-value: p=<5x10^-8
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.
Franceschini et al. (2018) conducted a meta-analysis in Subclinical atherosclerosis (n=71,128). Genetic variants (SNPs) vs. Reference alleles was evaluated on Genome-wide significant loci for cIMT and carotid plaque (p=<5x10^-8). A GWAS meta-analysis identified eight novel susceptibility loci for carotid intima-media thickness and one novel locus for carotid plaque, demonstrating significant genetic correlations with coronary heart disease and stroke.