Research Article| Volume 58, P217-222, March 2023

Causal association between iron deficiency anemia and chronic obstructive pulmonary disease: A bidirectional two-sample Mendelian randomization study

Published:January 09, 2023DOI:


      • The first bidirectional two-sample MR study to assess the causal association between IDA and COPD.
      • We found evidence of a causal relationship between IDA and COPD risk.
      • Mendelian randomization analysis has the advantage of providing a more reliable causality analysis, which is not available in general observational studies.



      Observational studies have found an association between iron deficiency anemia (IDA) and chronic obstructive pulmonary disease (COPD) risk. However, whether IDA plays a role in COPD development remains unclear.


      This study was performed to explore the causal association between IDA and COPD.


      We obtained summary statistics for IDA from 6087 cases and 211,115 controls of European ancestry in an open genome-wide association study (GWAS) to select strongly associated single nucleotide polymorphisms that could serve as instrumental variables for IDA (P < 5 × 10–8). Additional summary statistics for COPD were obtained from 6915 COPD cases and 186,723 controls of European ancestry from a publicly available GWAS. A bidirectional Mendelian randomization analysis was performed using inverse variance weighting as the primary method of analysis. The reliability of the results was verified by heterogeneity and sensitivity analysis.


      IDA increased the risk of COPD, with an odds ratio (OR) of 1.15 (95% confidence interval (CI: 1.04–1.25, p = 0.002). There was no evidence of a causal effect of COPD on IDA risk, with an OR of 0.99 (95% CI: 0.87–1.13, p = 0.91). The sensitivity analysis showed no evidence of heterogeneity or horizontal pleiotropy.


      We found that IDA increases the risk of COPD. Additionally, there was no evidence that COPD increases the risk of IDA. Therefore, IDA should be considered in future COPD risk studies and reintroduced as a potential therapeutic target. The relationship between COPD and IDA risk requires further study using indirect mechanisms.



      IDA (iron deficiency anemia), COPD (chronic obstructive pulmonary disease), MR (Mendelian randomization), GV (genetic variants), IV (instrumental variables), SNP (single nucleotide polymorphism), GWAS (genome-wide association study), IVW (inverse variance weighing), IL (interleukin)
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