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

Strawbridge, R. J. et al. (2020) Carotid intima-media thickness: novel loci, sex-specific effects, and genetic correlations with obesity and glucometabolic traits in UK Biobank. Arteriosclerosis, Thrombosis, and Vascular Biology, 40(2), pp. 446-461. (doi: 10.1161/ATVBAHA.119.313226) (PMID:31801372) (PMCID:PMC6975521)

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: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Daniel and Cullen, Dr Breda and Graham, Dr Nicholas and Ferguson, Ms Amy and Pearsall, Dr Robert and Lyall, Dr Laura and Bailey, Dr Mark and Shaw, Dr Richard and Ward, Dr Joey and Johnston, Ms Keira and Tank, Rachana and Pell, Professor Jill and Lyall, Dr Donald and Strawbridge, Dr Rona
• 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 > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health; College of Medical Veterinary and Life Sciences > School of Life Sciences; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• 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 40(2):446-461
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302131		Understanding the excess risk of cardiometabolic disease in individuals with serious mental illness	Jill Pell	Medical Research Council (MRC)	MR/S003061/1	HW - Public Health
173558		Polygenic risk for neuroticism and response to antidepressants in major depressive disorder New Title: Towards precision medicine for depressive disorders:	Joey Ward	Royal College of Physicians of Edinburgh (RCPE)	Ward, Mr Joey	HW - Mental Health and Wellbeing
190660		MRC Doctoral Training Grant 2013/14 and 2014/15	George Baillie	Medical Research Council (MRC)	MR/K501335/1	MVLS - Graduate School
173096		Investigating comorbidity between hypertension and bipolar disorder to identify new and repurposed medications for bipolar disorder	Daniel Smith	Lister Institute of Preventive Medicine (LISTININ)	Research Prize 2016	HW - Mental Health and Wellbeing
302957		Mental Health Data Pathfinder	Daniel Smith	Medical Research Council (MRC)	MC_PC_17217	HW - Mental Health and Wellbeing