OBJECTIVE HDL (high-density lipoprotein) cholesterol (HDL-C) and LDL (low-density lipoprotein) cholesterol (LDL-C) are inversely associated with infectious hospitalizations. Whether these represent causal relationships is unknown. Approach and Results: Adults of 40 to 69 years of age were recruited from across the United Kingdom between 2006 and 2010 and followed until March 31, 2016, as part of the UK Biobank. We determined HDL-C, LDL-C, and triglyceride polygenic scores for UK Biobank participants of British white ancestry (n=407 558). We examined the association of lipid levels and polygenic scores with infectious hospitalizations, antibiotic usage, and 28-day sepsis survival using Cox proportional hazards or logistic regression models. Measured levels of HDL-C and LDL-C were inversely associated with risk of infectious hospitalizations, while triglycerides displayed a positive association. A 1-mmol/L increase in genetically determined levels of HDL-C associated with a hazard ratio for infectious disease of 0.84 ([95% CI, 0.75-0.95]; P=0.004). Mendelian randomization using genetic variants associated with HDL-C as an instrumental variable was consistent with a causal relationship between elevated HDL-C and reduced risk of infectious hospitalizations (inverse weighted variance method, P=0.001). Furthermore, of 3222 participants who experienced an index episode of sepsis, there was a significant inverse association between continuous HDL-C polygenic score and 28-day mortality (adjusted hazard ratio, 0.37 [95% CI, 0.14-0.96] per 1 mmol/L increase; P=0.04). LDL-C and triglyceride polygenic scores were not significantly associated with hospitalization for infection, antibiotic use, or sepsis mortality. CONCLUSIONS Our results provide causal inference for an inverse relationship between HDL-C, but not LDL-C or triglycerides, and risk of an infectious hospitalization.

中文翻译：

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遗传确定的高密度脂蛋白胆固醇水平和传染病风险的因果推论。

目的HDL（高密度脂蛋白）胆固醇（HDL-C）和LDL（低密度脂蛋白）胆固醇（LDL-C）与传染性住院成反比。这些是否代表因果关系尚不清楚。方法和结果：2006年至2010年间，从英国各地招募40至69岁的成年人，并一直追踪到2016年3月31日，作为UK Biobank的一部分。我们确定了英国白血统的英国生物库参与者（n = 407 558）的HDL-C，LDL-C和甘油三酸酯多基因评分。我们使用Cox比例风险或Logistic回归模型研究了血脂水平和多基因评分与感染性住院，抗生素使用和28天脓毒症生存率的关系。HDL-C和LDL-C的测定水平与感染性住院风险呈负相关，而甘油三酸酯显示出正相关。遗传学上确定的HDL-C水平升高1 mmol / L，与传染病风险比相关，为0.84（[95％CI，0.75-0.95]; P = 0.004）。使用与HDL-C相关的遗传变异作为工具变量的孟德尔随机化与HDL-C升高与传染性住院风险降低之间的因果关系一致（逆加权方差法，P = 0.001）。此外，在3222名经历了败血症指数发作的参与者中，持续的HDL-C多基因评分与28天死亡率之间存在显着的负相关性（调整后的危险比，每1 mmol / L 0.37 [95％CI，0.14-0.96]） L增加； P = 0.04）。LDL-C和甘油三酸酯多基因评分与感染，抗生素使用，或败血症死亡率。结论我们的结果为HDL-C（而非LDL-C或甘油三酸酯）与感染性住院风险之间的反比关系提供了因果关系。