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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.

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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.
School of Life Sciences, College of Medical, Veterinary and Life Sciences (M.E.S.B., K.J.A.J.), University of Glasgow, United Kingdom.
Division of Psychiatry, College of Medicine, University of Edinburgh, United Kingdom (K.J.A.J.).
Health Data Research United Kingdom (R.J.S.).
Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (R.J.S.).



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.


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.


atherosclerosis; carotid artery; coronary artery disease; diabetes, type 2; genetics, association studies; intima-media thickness; obesity


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