Carotid Intima-Media Thickness: Novel Loci, Sex-Specific Effects, and Genetic Correlations With Obesity and Glucometabolic Traits in UK Biobank

Arterioscler Thromb Vasc Biol. 2020 Feb;40(2):446-461. doi: 10.1161/ATVBAHA.119.313226. Epub 2019 Dec 5.


Objective: Atherosclerosis is the underlying cause of most cardiovascular disease, but mechanisms underlying atherosclerosis are incompletely understood. Ultrasound measurement of the carotid intima-media thickness (cIMT) can be used to measure vascular remodeling, which is indicative of atherosclerosis. Genome-wide association studies have identified many genetic loci associated with cIMT, but heterogeneity of measurements collected by many small cohorts have been a major limitation in these efforts. Here, we conducted genome-wide association analyses in UKB (UK Biobank; N=22 179), the largest single study with consistent cIMT measurements. Approach and Results: We used BOLT-LMM software to run linear regression of cIMT in UKB, adjusted for age, sex, and genotyping chip. In white British participants, we identified 5 novel loci associated with cIMT and replicated most previously reported loci. In the first sex-specific analyses of cIMT, we identified a locus on chromosome 5, associated with cIMT in women only and highlight VCAN as a good candidate gene at this locus. Genetic correlations with body mass index and glucometabolic traits were also observed. Two loci influenced risk of ischemic heart disease.

Conclusions: These findings replicate previously reported associations, highlight novel biology, and provide new directions for investigating the sex differences observed in cardiovascular disease presentation and progression.

Keywords: atherosclerosis; carotid artery; coronary artery disease; diabetes, type 2; genetics, association studies; intima-media thickness; obesity.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Specimen Banks / statistics & numerical data*
  • Body Mass Index
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / genetics*
  • Carotid Arteries / diagnostic imaging*
  • Carotid Intima-Media Thickness*
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / epidemiology
  • Obesity / genetics*
  • Phenotype
  • Risk Assessment
  • Risk Factors
  • United Kingdom / epidemiology
  • Vascular Remodeling / physiology*