Atherosclerosis is a polygenic disorder that often affects multiple arteries. Carotid arteries are common sites for evaluating subclinical atherosclerosis, and aortic root is the standard site for quantifying atherosclerosis in mice. We compared genetic control of atherosclerosis between the two sites in the same cohort derived from two phenotypically divergent Apoe-null (Apoe^–/–) mouse strains. Female F2 mice were generated from C57BL/6 (B6) and C3H/He (C3H) Apoe^–/– mice and fed 12 weeks of Western diet. Atherosclerotic lesions in carotid bifurcation and aortic root and plasma levels of fasting lipids and glucose were measured. 153 genetic markers across the genome were typed. All F2 mice developed aortic atherosclerosis, while 1/5 formed no or little carotid lesions. Genome-wide scans revealed 3 significant loci on chromosome (Chr) 1, Chr15, 6 suggestive loci for aortic atherosclerosis, 2 significant loci on Chr6, Chr12, and 6 suggestive loci for carotid atherosclerosis. Only 2 loci for aortic lesions showed colocalization with loci for carotid lesions. Carotid lesion sizes were moderately correlated with aortic lesion sizes (r = 0.303; P = 4.6E-6), but they showed slight or no association with plasma HDL, non-HDL cholesterol, triglyceride, or glucose levels among F2 mice. Bioinformatics analyses prioritized Cryge as a likely causal gene for Ath30, Cdh6 and Dnah5 as causal genes for Ath22. Our data demonstrate vascular site-specific effects of genetic factors on atherosclerosis in the same animals and highlight the need to extend studies of atherosclerosis to sites beyond aortas of mice.

动脉粥样硬化是一种多基因性疾病，通常会影响多条动脉。颈动脉是评估亚临床动脉粥样硬化的常见部位，而主动脉根是量化小鼠动脉粥样硬化的标准部位。我们比较了来自两个表型不同的Apoe -null（Apoe ^-/-）小鼠品系的同一队列中两个部位之间的动脉粥样硬化的遗传控制。从C57BL / 6（B6）和C3H / He（C3H）Apoe产生雌性F2小鼠^-/-小鼠，喂食12周的西方饮食。测量了颈动脉分叉处和主动脉根的动脉粥样硬化病变以及空腹脂质和葡萄糖的血浆水平。在整个基因组中输入了153个遗传标记。所有F2小鼠都发展为主动脉粥样硬化，而1/5则没有或几乎没有形成颈动脉病变。全基因组扫描显示，在染色体（Chr）1，Chr15上有3个显着位点，在主动脉粥样硬化中有6个暗示位点，在Chr6，Chr12上有2个显着位点，而在颈动脉粥样硬化中有6个暗示位点。仅2个主动脉病变位点显示与颈动脉病变位点共定位。颈动脉病变大小与主动脉病变大小呈中等相关性（r = 0.303；p= 4.6E-6），但在F2小鼠中它们与血浆HDL，非HDL胆固醇，甘油三酸酯或葡萄糖水平无相关性。生物信息学分析优先Cryge作为一个可能的致病基因Ath30，CDH6和Dnah5作为因果基因Ath22。我们的数据证明了遗传因素对同一动物中动脉粥样硬化的血管部位特异性作用，并突出了将动脉粥样硬化研究扩展到小鼠主动脉以外的部位的必要性。