Genetically diverse outbred mice allow for the study of genetic variation in the context of high dietary and environmental control. Using a machine learning approach, we investigated clinical and morphometric factors that associate with serum cholesterol levels in 840 genetically unique Diversity Outbred mice of both sexes (n = 417 male and 423 female), and on both a control chow (% kcals in diet: protein 22%, carbohydrate 62%, fat 16%, no cholesterol) and high fat high sucrose (% kcals in diet: protein 15%, carbohydrate 41%, fat 45%, 0.05% cholesterol). We find expected elevations of cholesterol in male mice, as well as in mice with elevated serum triglycerides and/or fed a high fat high sucrose diet. The third strongest predictor was serum calcium which correlated with serum cholesterol across both diets and sexes (r = 0.39–0.48) in both Diversity Outbred (P = 3.0 × 10⁻⁴³) and BXD (P = 0.005) mice. This is in-line with several human cohort studies which show associations between calcium and cholesterol, and calcium as an independent predictor of cardiovascular events.

中文翻译：

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遗传多样性小鼠品系中血液胆固醇和钙水平之间的横截面关联

遗传多样性的远交小鼠可以在高饮食和环境控制的背景下研究遗传变异。使用机器学习方法，我们研究了与 840 只基因独特的多样性远交小鼠（n  = 417 只雄性和 423 只雌性）以及对照饲料（饮食中的千卡百分比：蛋白质22％，碳水化合物62％，脂肪16％，无胆固醇）和高脂肪高蔗糖（饮食中％kcals：蛋白质15％，碳水化合物41％，脂肪45％，0.05％胆固醇）。我们发现雄性小鼠以及血清甘油三酯升高和/或喂食高脂肪高蔗糖饮食的小鼠的胆固醇预期升高。 第三个最强的预测因子是血清钙，在 Diversity Outbred ( P  = 3.0 × 10 ^-43 ) 和 BXD ( P  = 0.005) 小鼠中，血清钙与饮食和性别之间的血清胆固醇相关 ( r = 0.39–0.48)。这与几项人类队列研究一致，这些研究表明钙和胆固醇之间存在关联，并且钙是心血管事件的独立预测因子。