HIV infection and risk of COPD: a two-sample Mendelian randomization study

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Background: The causal relationship between HIV infection and COPD remains unclear, with some studies suggesting an elevated risk in HIV-infected individuals, while others show no correlation, particularly in female patients. Objectives: This study assessed the causal relationship between HIV infection and COPD using a two-sample Mendelian randomization (MR) approach, exploring whether HIV increases the risk of COPD, including early-onset and late-onset COPD. Methods: This study selected instrumental variables (IVs) significantly associated with HIV infection (P<5×10-6, linkage disequilibrium <0.001, genetic distance = 10,000 KB) and excluded those associated with confounders. Two-sample MR analysis was conducted using pooled data from GWAS and the FinnGen project. IVs were evaluated using IVW, Mr-Egger, and weighted median methods. Sensitivity analyses included Cochran’s Q test, Mr-Presso, Mr-Egger regression, and leave-one-out analysis. Results: Based on 6 selected SNPs with F-values >10, MR analyses found no significant causal relationship between HIV infection and COPD, early-onset COPD, or late-onset COPD. IVW, MR-Egger, and weighted median methods consistently showed p-values >0.05, with ORs near 1. Cochran's Q test indicated no heterogeneity between IVs, while MR-Egger regression suggested horizontal pleiotropy for COPD and early-onset COPD but not for late-onset COPD. Leave-one-out analysis showed that no SNP had a significant impact on the results. Conclusions: This study suggests that HIV infection and COPD are unlikely to be causally linked. This relationship may be driven by shared risk factors or treatment effects.

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