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Abstract
Low levels of blood cholesterol are known to be associated with increased risk of infectious disease. However, it remains unclear if this relationship is causal in nature. This study assessed the influence of common variants associated with blood lipid levels on infectious disease risk in individuals of British Caucasian ancestry from the UK Biobank. Using genetic variants as risk factors can circumvent many issues of confounding and reverse causation and has the potential to provide causal inference regarding the effect of genetically determined lipid levels on susceptibility to infectious disease. Elevated levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were observationally associated with reduced risk of infectious disease hospitalizations. For genetically determined lipid levels, only high-density lipoprotein cholesterol was significantly associated with reduced risk of hospitalizations for infectious disease, lower odds of outpatient antibiotic usage, and reduced risk of mortality from sepsis. Mendelian randomization analysis suggested that the observational relationship between higher levels of high-density lipoprotein cholesterol and reduced risk of hospitalization for infectious disease could be causal in nature. Our results provide causal inference for an inverse relationship between high-density lipoprotein cholesterol, but not low-density lipoprotein-cholesterol or triglycerides, and risk of an infectious hospitalization.