Highlights
- •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.
Abstract
Background
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.
Objectives
This study was performed to explore the causal association between IDA and COPD.
Methods
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.
Results
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.
Conclusions
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.
Keywords
Abbreviations:
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)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 09, 2023
Accepted:
January 3,
2023
Received in revised form:
December 29,
2022
Received:
November 26,
2022
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
