Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep 6;14(18):3683.
doi: 10.3390/nu14183683.

Genetic Causal Association between Iron Status and Osteoarthritis: A Two-Sample Mendelian Randomization

Jiawen Xu  1 , Shaoyun Zhang  1   2 , Ye Tian  3 , Haibo Si  1 , Yi Zeng  1 , Yuangang Wu  1 , Yuan Liu  1 , Mingyang Li  1 , Kaibo Sun  1 , Limin Wu  1 , Bin Shen  1
Affiliations

Genetic Causal Association between Iron Status and Osteoarthritis: A Two-Sample Mendelian Randomization

Jiawen Xu et al. Nutrients. .

Abstract

Objective: Observational studies have shown the association between iron status and osteoarthritis (OA). However, due to difficulties of determining sequential temporality, their causal association is still elusive. Based on the summary data of genome-wide association studies (GWASs) of a large-scale population, this study explored the genetic causal association between iron status and OA. Methods: First, we took a series of quality control steps to select eligible instrumental SNPs which were strongly associated with exposure. The genetic causal association between iron status and OA was analyzed using the two-sample Mendelian randomization (MR). Inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were used for analysis. The results were mainly based on IVW (random effects), followed by sensitivity analysis. IVW and MR-Egger were used for heterogeneity testing. MR-Egger was also used for pleiotropy testing. Leave-one-SNP-out analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Maximum likelihood, penalized weighted median, and IVW (fixed effects) were performed to further validate the reliability of results. Results: IVW results showed that transferrin saturation had a positive causal association with knee osteoarthritis (KOA), hip osteoarthritis (HOA) and KOA or HOA (p < 0.05, OR > 1), and there was a negative causal association between transferrin and HOA and KOA or HOA (p < 0.05, OR < 1). The results of heterogeneity test showed that our IVW analysis results were basically free of heterogeneity (p > 0.05). The results of the pleiotropy test showed that there was no pleiotropy in our IVW analysis (p > 0.05). The analysis results of maximum likelihood, penalized weighted median and IVW (fixed effects) were consistent with our IVW results. No genetic causal association was found between serum iron and ferritin and OA. Conclusions: This study provides evidence of the causal association between iron status and OA, which provides novel insights to the genetic research of OA.

Keywords: Mendelian randomization; causal association; genetic analyses; osteoarthritis.

PubMed Disclaimer

Conflict of interest statement

All authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
MR results of transferrin saturation and knee osteoarthritis (KOA): (A) scatter plot of genetic correlations of transferrin saturation and KOA using different MR methods. The slopes of line represent the causal effect of each method, respectivel; (B) forest plot of the causal effects of transferrin saturation associated SNPs on KOA. The red and black dot/bar indicate the causal estimate of transferrin saturation level on risk of patients with KOA.
Figure 2
Figure 2
MR results of transferrin saturation, transferrin and hip osteoarthritis (HOA): (A) scatter plot of genetic correlations of transferrin saturation and HOA using different MR methods. The slopes of line represent the causal effect of each method, respectively; (B) forest plot of the causal effects of transferrin saturation associated SNPs on HOA; (C) scatter plot of genetic correlations of transferrin and HOA using different MR methods. The slopes of line represent the causal effect of each method, respectively; and (D) forest plot of the causal effects of transferrin associated SNPs on HOA. (B): The red and black dot/bar indicate the causal estimate of transferrin saturation level on risk of patients with HOA. (D): The red and black dot/bar indicate the causal estimate of transferrin level on risk of patients with HOA.
Figure 3
Figure 3
MR results of transferrin saturation, transferrin and knee/hip osteoarthritis (K/HOA): (A) scatter plot of genetic correlations of transferrin saturation and K/HOA using different MR methods. The slopes of line represent the causal effect of each method, respectively; (B) forest plot of the causal effects of transferrin saturation associated SNPs on K/HOA; (C) scatter plot of genetic correlations of transferrin and K/HOA using different MR methods. The slopes of line represent the causal effect of each method, respectively; and (D) forrest plot of the causal effects of transferrin associated SNPs on K/HOA. (B): The red and black dot/bar indicate the causal estimate of transferrin saturation level on risk of patients with K/HOA. (D): The red and black dot/bar indicate the causal estimate of transferrin level on risk of patients with K/HOA.
Figure 4
Figure 4
Estimated causal effects between iron status indicator and OA using different MR methods.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hunter D.J., Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393:1745–1759. doi: 10.1016/S0140-6736(19)30417-9. - DOI - PubMed
    1. Hunter D.J., March L., Chew M. Osteoarthritis in 2020 and beyond: A Lancet Commission. Lancet. 2020;396:1711–1712. doi: 10.1016/S0140-6736(20)32230-3. - DOI - PubMed
    1. Mandl L. Osteoarthritis year in review 2018: Clinical. Osteoarthr. Cartil. 2019;27:359–364. doi: 10.1016/j.joca.2018.11.001. - DOI - PubMed
    1. Liu L., Wang S., Wen Y., Li P., Cheng S., Ma M., Zhang L., Cheng B., Qi X., Liang C., et al. Assessing the genetic relationships between osteoarthritis and human plasma proteins: A large scale genetic correlation scan. Ann. Transl. Med. 2020;8:677. doi: 10.21037/atm-19-4643. - DOI - PMC - PubMed
    1. Meng H., Jiang L., Song Z., Wang F. Causal Associations of Circulating Lipids with Osteoarthritis: A Bidirectional Mendelian Randomization Study. Nutrients. 2022;14:1327. doi: 10.3390/nu14071327. - DOI - PMC - PubMed

LinkOut - more resources