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  • Title: Carotid Intima-Media Thickness: Novel Loci, Sex-Specific Effects, and Genetic Correlations With Obesity and Glucometabolic Traits in UK Biobank.
    Author: Strawbridge RJ, Ward J, Bailey MES, Cullen B, Ferguson A, Graham N, Johnston KJA, Lyall LM, Pearsall R, Pell J, Shaw RJ, Tank R, Lyall DM, Smith DJ.
    Journal: Arterioscler Thromb Vasc Biol; 2020 Feb; 40(2):446-461. PubMed ID: 31801372.
    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. 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.
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