Rxivist logo

Carotid intima-media thickness in UK Biobank: Identification of novel genome-wide loci, sex-specific effects and genetic correlations with obesity and glucometabolic traits.

By Rona J Strawbridge, Joey Ward, Mark E S Bailey, Breda Cullen, Amy Ferguson, Nicholas Graham, Keira J.A. Johnston, Laura M. Lyall, Robert Pearsall, Jill Pell, Richard John Shaw, Rachana Tank, Donald M. Lyall, Daniel J Smith

Posted 30 Jul 2019
bioRxiv DOI: 10.1101/718684

Objectives: Atherosclerosis is the underlying cause of most cardiovascular disease, but mechanisms underlying atherosclerosis are incompletely understood. Ultra-sound measurement of the carotid artery intima-media thickness (cIMT) can be used to measure vascular remodelling, which is indicative of atherosclerosis. Genome-wide association studies have identified a number of 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 UK Biobank (N=22,179), the largest single study with consistent cIMT measurements. Approach and results: We used BOLT-LMM to run linear regression of cIMT in UK Biobank, adjusted for age, sex, genotyping platform and population structure. In white British participants, we identified 4 novel loci associated with cIMT and replicated most previously reported loci. In the first sex-specific analyses of cIMT, we identified a female-specific 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. Conclusion: 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.

Download data

  • Downloaded 667 times
  • Download rankings, all-time:
    • Site-wide: 52,823
    • In genetics: 2,215
  • Year to date:
    • Site-wide: None
  • Since beginning of last month:
    • Site-wide: 68,720

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News