Carotid intima-media thickness: novel loci, sex-specific effects, and genetic correlations with obesity and glucometabolic traits in UKB

Strawbridge, R. J. et al. (2019) Carotid intima-media thickness: novel loci, sex-specific effects, and genetic correlations with obesity and glucometabolic traits in UKB. Arteriosclerosis, Thrombosis, and Vascular Biology, (doi:10.1161/ATVBAHA.119.313226) (PMID:31801372) (Early Online Publication)

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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 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.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Shaw, Dr Richard and Ferguson, Ms Amy and Ward, Mr Joey and Johnston, Ms Keira and Cullen, Dr Breda and Pearsall, Dr Robert and Smith, Professor Daniel and Tank, Rachana and Pell, Professor Jill and Lyall, Dr Laura and Bailey, Dr Mark and Lyall, Dr Donald and Strawbridge, Dr Rona and Graham, Dr Nicholas
Authors: Strawbridge, R. J., Ward, J., Bailey, M. E.S., Cullen, B., Ferguson, A., Graham, N., Johnston, K. J.A., Lyall, L. M., Pearsall, R., Pell, J., Shaw, R. J., Tank, R., Lyall, D. M., and Smith, D. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN:1079-5642
ISSN (Online):1524-4636
Published Online:05 December 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Arteriosclerosis, Thrombosis, and Vascular Biology 2019
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
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