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
. 2024 Apr;114(4):386-396.
doi: 10.1007/s00223-024-01190-8. Epub 2024 Feb 14.

The Relationship Between Systemic Lupus Erythematosus and Osteoporosis Based on Different Ethnic Groups: a Two-Sample Mendelian Randomization Analysis

Y K Shi #  1 , K H Yuan #  1 , Z M Fu  1 , R R Hu  1 , H Wang  2
Affiliations

The Relationship Between Systemic Lupus Erythematosus and Osteoporosis Based on Different Ethnic Groups: a Two-Sample Mendelian Randomization Analysis

Y K Shi et al. Calcif Tissue Int. 2024 Apr.

Abstract

The previous observational studies could not overcome the effects of confounding variables and reverse causality. We aimed to determine whether there is a causal relationship between systemic lupus erythematosus and osteoporosis in East Asian and European populations, respectively, by two-sample Mendelian Randomization analysis. We obtained and downloaded data from publicly available genome-wide association study databases and analyses for East Asian and European populations, including systemic lupus erythematosus (SLE), osteoporosis (OP), multisite bone mineral density (BMD), and OP with fracture. After screening for instrumental single-nucleotide polymorphisms (SNPs) significantly correlated to SLE, the inverse-variance weighted (IVW) method was used for calculating the ratio and 95% confidence interval, besides utilizing MR-Egger, weighted median, and weighted mode to assess the robustness of the primary outcome. Moreover, multiple analyses, including MR-PRESSO, MR-Egger intercept, Cochran's Q test, as well as "leave-one-out" sensitivity, were used for evaluating horizontal pleiotropy, heterogeneity, and stability. Finally, we exchanged exposure and outcome and performed a reverse MR analysis. IVW (OR = 1.05, 95% CI = 1.01-1.09, P = 0.009) indicated a significant positive correlation between genetically predicted SLE and OP in East Asians. Furthermore, neither heterogeneity nor horizontal pleiotropy was observed. In Europe, there was no significant genetically predicted causal relation between SLE and OP. Bi-directional MR analysis showed no reverse causality between SLE and OP. In the East Asian population, genetically predicted SLE may have had a positive causal relationship with OP. In Europe, there is insufficient evidence for a potential causal relation between SLE and OP or BMD and fracture, and the correlations currently observed may be attributed to a variety of confounder variables.

Keywords: Mendelian randomization; Osteoporosis; Systemic lupus erythematosus.

PubMed Disclaimer

References

    1. Chin KY, Ng BN, Rostam MKI, Muhammad Fadzil NFD, Raman V, Mohamed Yunus F, Syed Hashim SA, Ekeuku SO (2022) A Mini review on osteoporosis: from biology to pharmacological management of bone loss. J Clin Med 11(21):6434. https://doi.org/10.3390/jcm11216434 - DOI - PubMed - PMC
    1. Zhu X, Bai W, Zheng H (2021) Twelve years of GWAS discoveries for osteoporosis and related traits: advances, challenges and applications. Bone Res 9(1):23. https://doi.org/10.1038/s41413-021-00143-3 - DOI - PubMed - PMC
    1. Huang X, Zhang Q, Zhang H, Lu Q (2022) A contemporary update on the diagnosis of systemic lupus erythematosus. Clin Rev Allergy Immunol 63(3):311–329. https://doi.org/10.1007/s12016-021-08917-7 - DOI - PubMed
    1. Barber MRW, Drenkard C, Falasinnu T, Hoi A, Mak A, Kow NY, Svenungsson E, Peterson J, Clarke AE, Ramsey-Goldman R (2021) Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol 17(10):642. https://doi.org/10.1038/s41584-021-00690-3 - DOI - PubMed
    1. Xia J, Luo R, Guo S, Yang Y, Ge S, Xu G, Zeng R (2019) Prevalence and risk factors of reduced bone mineral density in systemic lupus erythematosus patients: a meta-analysis. Biomed Res Int 2019:3731648. https://doi.org/10.1155/2019/3731648 - DOI - PubMed - PMC

MeSH terms

LinkOut - more resources