Lipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization study

Observational studies have identified a possible connection between lipid-lowering medications and respiratory illnesses. However, it remains unclear whether lipid-lowering drugs is causative for respiratory diseases, and we aimed to answer this question.

We performed Mendelian randomization (MR) analyses by integrating data from genome-wide association studies (GWAS). Three statistical approaches were employed for MR analysis: inverse variance weighting (IVW), MR-Egger, and weighted median. The purpose was to evaluate the causal relationships between 10 drug targets that lower lipid levels and the likelihood of developing 7 respiratory diseases. Additional sensitivity analyses were conducted to ensure the robustness and validity of the results.

After adjusting for multiple testing, our MR analysis identified APOB (odd ratios [OR]: 0.86; 95% confidence interval [CI]: 0.77 to 0.97; P_IVW = 0.01) and PCSK9 (OR: 0.84; 95% CI: 0.72 to 0.97; P_IVW = 0.02) as significant risk targets for asthma. Additionally, LDLR was found to be a significant risk target for chronic obstructive pulmonary disease (OR: 0.81; 95% CI: 0.67 to 0.98; P_IVW = 0.03). The sensitivity analysis validated no proof of heterogeneity or pleiotropy amongst the mentioned results.

Our findings suggest a likely causal relationship between respiratory diseases and lipid-lowering drug targets. Further mechanistic and clinical research is needed to confirm and validate these findings.