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.

中文翻译：

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英国生物库中颈动脉内膜中层厚度：新位点、性别特异性效应以及与肥胖和糖代谢特征的遗传相关性。


目的 动脉粥样硬化是大多数心血管疾病的根本原因，但动脉粥样硬化的机制尚不完全清楚。颈动脉内膜中层厚度（cIMT）的超声测量可用于测量血管重塑，这表明动脉粥样硬化。全基因组关联研究已经确定了许多与 cIMT 相关的遗传位点，但许多小群体收集的测量结果的异质性一直是这些努力的主要限制。在这里，我们在 UKB（英国生物银行；N=22 179）中进行了全基因组关联分析，这是具有一致 cIMT 测量值的最大单一研究。方法和结果：我们使用 BOLT-LMM 软件对 UKB 中的 cIMT 进行线性回归，并根据年龄、性别和基因分型芯片进行调整。在英国白人参与者中，我们确定了 5 个与 cIMT 相关的新基因座，并复制了大多数先前报告的基因座。在 cIMT 的首次性别特异性分析中，我们鉴定了 5 号染色体上的一个位点，该位点仅与女性中的 cIMT 相关，并强调 VCAN 是该位点的良好候选基因。还观察到与体重指数和糖代谢特征的遗传相关性。两个基因座影响缺血性心脏病的风险。结论 这些发现重复了之前报道的关联，强调了新颖的生物学，并为研究心血管疾病表现和进展中观察到的性别差异提供了新的方向。