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

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.

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