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

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

Author information

1
From the Institute of Health and Wellbeing (R.J.S., J.W., B.C., A.F., N.G., K.J.A.J., L.M.L., R.P., J.P., R.J.S., R.T., D.M.L., D.J.S.), University of Glasgow, United Kingdom.
2
School of Life Sciences, College of Medical, Veterinary and Life Sciences (M.E.S.B., K.J.A.J.), University of Glasgow, United Kingdom.
3
Division of Psychiatry, College of Medicine, University of Edinburgh, United Kingdom (K.J.A.J.).
4
Health Data Research United Kingdom (R.J.S.).
5
Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (R.J.S.).

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‚ÄČ179), 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

PMID:
31801372
DOI:
10.1161/ATVBAHA.119.313226

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