Abstract
Mitochondrial DNA copy number (mtDNA-CN) play a pivotal role in Lung cancer (LC). However, it is not clear that the relationship between exposure and outcome. Therefore, our database were obtained from a genome-wide association study (GWAS) summary statistics. By the univariate and multivariate bidirectional Mendelian randomization (MR), the results indicate that forward MR analysis showing that mtDNA-CN increased the risk of LC (IVW OR = 1.32, 95% CI: 1.08–1.61, P = 0.006; BW OR = 1.37, 95% CI: 1.12–1.68, P = 0.002). The results are consistent with subgroup. However, there was no statistical significance in reverse MR analysis. The mtDNA-CN was still at risk for LC after multivariate MR adjustment for confounders (IVW OR = 1.40, 95%CI: 1.13–1.75, P = 0.003; FDR adjust p = 0.005). Subgroup analysis suggest the same conclusion in multivariate MR Analysis. Sensitivity analyses found no evidence of horizontal pleiotropy and heterogeneity. In this study, it was found that mtDNA-CN can predict the risk of LC, especially in smokers. However, we did not find a reverse causal relationship. This imply that mtDNA-CN can be used as a biomarker in the clinical practice of LC.