- •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.
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
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Heart & Lung: The Journal of Cardiopulmonary and Acute Care
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Chronic obstructive pulmonary disease.Lancet. 2017; 389: 1931-1940
- Chronic obstructive pulmonary disease (COPD).Am J Respir Crit Care Med. 2019; 199: P1-P2
- Chronic obstructive pulmonary disease.Ann Intern Med. 2020; 173: Itc17-itc32
- Chronic obstructive pulmonary disease: evaluation and management.Med Clin N Am. 2019; 103: 453-461
- Chronic obstructive pulmonary disease.Crit Care Nurs Q. 2016; 39: 124-130
- Chronic obstructive pulmonary disease in China: a nationwide prevalence study.Lancet Respir Med. 2018; 6: 421-430
- New insights into iron deficiency and iron deficiency anemia.Blood Rev. 2017; 31: 225-233
- Iron deficiency anemia: evaluation and management.Am Fam Physician. 2013; 87: 98-104
- Iron-deficiency anemia.N Engl J Med. 2015; 372: 1832-1843
- Iron deficiency anemia.Med Clin N Am. 2017; 101: 319-332
- The Significance of iron deficiency and anemia in a real-life COPD cohort.Int J Med Sci. 2020; 17: 2232-2239
- Iron deficiency in non-anemic chronic obstructive pulmonary disease in a predominantly male population: an ignored entity.Monaldi Arch Chest Dis. 2020; (= Archivio Monaldi per le malattie del torace): 90
- The impact of anaemia and iron deficiency in chronic obstructive pulmonary disease: a clinical overview.Rev Port Pneumol. 2017; 23: 146-155
- Anemia in chronic obstructive pulmonary disease and the potential role of iron deficiency.COPD. 2016; 13: 100-109
- Mendelian randomization.Cold Spring Harb Perspect Med. 2022; 12: a041302
- Meta-analysis and Mendelian randomization: a review.Res Synth Methods. 2019; 10: 486-496
- Mendelian randomization: genetic anchors for causal inference in epidemiological studies.Hum Mol Genet. 2014; 23: R89-R98
- Mendelian randomization as an approach to assess causality using observational data.J Am Soc Nephrol. 2016; 27: 3253-3265
- Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration.PLoS Med. 2007; 4: e297
- Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.Nat Genet. 2018; 50: 693-698
- The "Iron"-y of iron overload and iron deficiency in chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 2017; 196: 1103-1112
- Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial.BMJ Open Respir Res. 2020; 7e000577
- Iron lung versus mask ventilation in acute exacerbation of COPD: a randomised crossover study.Intensive Care Med. 2009; 35: 648-655
- Pathogenic triad in COPD: oxidative stress, protease-antiprotease imbalance, and inflammation.Int J Chron Obstruct Pulmon Dis. 2011; 6: 413-421
- Anemia in chronic obstructive pulmonary disease: prevalence, pathogenesis, and potential impact.Lung India. 2015; 32 (official organ of Indian Chest Society): 142-151
- Iron replacement and redox balance in non-anemic and mildly anemic iron deficiency COPD patients: insights from a clinical trial.Biomedicines. 2021; 9: 1191
- The potential impact of anaemia of chronic disease in COPD.Eur Respir J. 2006; 27: 390-396
- Anaemia in chronic obstructive pulmonary disease. Does it really matter?.Int J Clin Pract. 2013; 67: 558-565
Published online: January 09, 2023
Accepted: January 3, 2023
Received in revised form: December 29, 2022
Received: November 26, 2022
© 2023 Elsevier Inc. All rights reserved.