AIMS: Low levels of LDL cholesterol may be associated with risk of infectious disease. We tested the hypothesis that low LDL cholesterol due to genetic variation in the METHODS AND RESULTS: Using observational and Mendelian randomization designs, we examined associations of low plasma LDL cholesterol with risk of bacterial and viral infections in 119 805 individuals from the Copenhagen General Population Study/Copenhagen City Heart Study, 468 701 from the UK Biobank, and up to 376 773 from the FinnGen Research Project. Observationally, low LDL cholesterol concentrations were associated with risk of hospitalization for both bacterial and viral infections. In genetic analyses, a 1 mmol/L lower LDL cholesterol was associated with lower plasma PCSK9 {-0.55 nmol/L [95% confidence interval (CI): -1.06 to -0.05]
CONCLUSION: Genetically low LDL cholesterol concentrations were associated with lower concentration of markers of inflammation
lower risk of hospitalization for unspecified bacterial infections, infectious diarrhoeal diseases, bacterial pneumonia, and sepsis
and higher risk of viral infections and HIV/AIDS.