| Title: | Carotid Intima-Media Thickness |
| Journal: | Arteriosclerosis Thrombosis and Vascular Biology |
| Published: | 5 Dec 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31801372/ |
| DOI: | https://doi.org/10.1161/atvbaha.119.313226 |
| URL: | https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.119.313226 |
Publication 4429
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Abstract
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.</p>
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.</p>
19 Keywords
- Biological Specimen Banks
- Body Mass Index
- Cardiovascular Diseases
- Carotid Arteries
- Carotid Intima-Media Thickness
- Female
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Incidence
- Male
- Middle Aged
- Obesity
- Phenotype
- Risk Assessment
- Risk Factors
- United Kingdom
- Vascular Remodeling
14 Authors
- 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 J. Shaw
- Rachana Tank
- Donald M. Lyall
- Daniel J. Smith
Enabling scientific discoveries that improve human health