Genome-wide meta-analysis identifies novel loci of plaque burden in carotid artery

Atherosclerosis. 2017 Apr;259:32-40. doi: 10.1016/j.atherosclerosis.2017.02.018. Epub 2017 Feb 24.

Abstract

Background and aims: Carotid artery plaque is an established marker of subclinical atherosclerosis and common patho-mechanisms with coronary artery disease (CAD) are hypothesized. We aimed to identify genetic variants associated with carotid plaque and to examine the potential shared genetic basis with CAD.

Methods: After investigating the reliability of plaque detection, we performed a genome-wide meta-association study in two independent cohorts (LIFE-Adult, n = 4037 and LIFE-Heart, n = 3152) for carotid plaque score (PS), defined as the sum of the plaque load of common carotid artery and carotid bulb. Further, we analyzed whether previously reported CAD and stroke loci were also associated with PS.

Results: We identified two loci with genome-wide significance for PS. One locus is the known CAD-locus at chromosome 9p21 (lead SNP rs9644862, p = 8.73 × 10-12). We also describe a novel locus on chromosome 10q24 within the SFXN2 gene as the most probable candidate (lead SNP rs2902548, p = 1.97 × 10-8). In addition, 17 out of 58 known CAD loci and six of 17 known stroke loci were associated with PS at a nominal level of significance.

Conclusions: We showed that PS is a reliable trait to analyze genetics of atherosclerosis. Two new loci of genome-wide significant association with PS were found. The observed non-random overlap of CAD and PS associations strengthens the hypothesis of a shared genetic basis for these atherosclerotic manifestations.

Keywords: Atherosclerosis; Carotid artery plaque; Genome-wide association analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / pathology*
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / genetics*
  • Carotid Artery Diseases / pathology
  • Carotid Intima-Media Thickness
  • Cation Transport Proteins / genetics
  • Chromosomes, Human, Pair 10
  • Chromosomes, Human, Pair 9
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Plaque, Atherosclerotic*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Severity of Illness Index
  • Stroke / diagnostic imaging
  • Stroke / genetics*
  • Stroke / pathology

Substances

  • Cation Transport Proteins
  • SFXN2 protein, human