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Association between type 1 diabetes and systemic lupus erythematosus: a Mendelian randomization study

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Abstract

Objectives

Observational studies have shown that there is a bidirectional relationship between type 1 diabetes (T1D) and systemic lupus erythematosus (SLE); the causality of this association remains elusive and may be affected by confusion and reverse causality. There is also a lack of large-scale randomized controlled trials to verify. Therefore, this Mendelian randomization (MR) study aimed to investigate the causal association between T1D and SLE.

Methods

We aggregated data using publicly available genome-wide association studies (GWAS), all from European populations. Select independent (R2 < 0.001) and closely related to exposure (P < 5 × 10−8) as instrumental variables (IVs). The inverse-variance weighted (IVW) method was used as the primary method. We also used MR-Egger, the weighted median method, MR-Robust, MR-Lasso, and other methods leveraged as supplements.

Results

T1D had a positive causal association with SLE (IVW, odds ratio [OR] = 1.358, 95% confidence interval [CI], 1.205 − 1.530; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.137, 95% CI, 1.033 − 1.251; P = 0.001). SLE had a positive causal association with T1D (IVW, OR = 1.108, 95% CI, 1.074 − 1.144; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.085, 95% CI, 1.046 − 1.127; P < 0.001). These results have also been verified by sensitivity analysis.

Conclusion

The MR analysis results indicated a causal association between T1D and SLE. Therefore, further research is needed to clarify the potential biological mechanism between T1D and SLE.

Key Points

• Observational studies have shown that there is a bidirectional relationship between T1D and SLE.

• We evaluated causal effects between T1D and SLE by Mendelian randomization analyses.

• The MR analysis results indicated a causal association between T1D and SLE.

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Data availability

The GWAS summary datasets for SLE (GWAS ID: 26502338), are available through the open targets (https://genetics.opentargets.org). Type 1 diabetes (GWAS ID: GCST90000529), and Type 1 diabetes (GWAS ID: GCST90014023) are available through the ieu open gwas project (https://gwas.mrcieu.ac.uk/datasets).

Abbreviations

SLE :

Systemic lupus erythematosus

T1D :

Type 1 diabetes

IVs :

Instrumental variables

GWAS :

Genome-wide association study

SNP :

Single nucleotide polymorphism

MR :

Mendelian randomization

IVW :

Inverse-variance weighted

MR-Egger :

The Mendelian randomization-Egger

MR-PRESSO :

MR Pleiotropy RESidual Sum and Outlier

MR-RAPS :

MR-robust adjusted profile score

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Acknowledgements

F.X. conceived of the study idea. S.L. developed the theory and performed the computations. Y.Z., Q.Y., S.S., J.L., and verified the analytical methods. All authors discussed the results and contributed to the final manuscript.

Funding

This work was supported by the National Key Research and Development Program of China (2020YFC2003500), National Natural Science Foundation of China in 2021/general program (82173625), Shandong Province Key R&D Program (Science and Technology Demonstration Project) Project(2021SFGC0504).

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Authors and Affiliations

  1. Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Culture West Road, Jinan, 250012, Shandong, China

    Shulin Liu, Shucheng Si, Jiqing Li, Yingqi Zhao, Qingqing Yu & Fuzhong Xue

  2. Healthcare Big Data Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China

    Shulin Liu, Shucheng Si, Jiqing Li, Yingqi Zhao, Qingqing Yu & Fuzhong Xue

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Liu, S., Si, S., Li, J. et al. Association between type 1 diabetes and systemic lupus erythematosus: a Mendelian randomization study. Clin Rheumatol 43, 41–48 (2024). https://doi.org/10.1007/s10067-023-06800-8

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