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Assessing the Associations of Growth Differentiation Factor 15 with Rheumatic Diseases Using Genetic Data

Authors Ye D, Liu B, He Z, Huang L, Qian Y, Shao K, Wen C, Mao Y

Received 2 February 2021

Accepted for publication 11 March 2021

Published 23 March 2021 Volume 2021:13 Pages 245—252

DOI https://doi.org/10.2147/CLEP.S305024

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Vera Ehrenstein


Ding Ye,1 Bin Liu,1 Zhixing He,2 Lin Huang,2 Yu Qian,1 Keding Shao,2 Chengping Wen,2 Yingying Mao1

1Department of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of China

Correspondence: Yingying Mao
Department of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of China
Tel +86-571-8661-3536
Email [email protected]
Chengping Wen
Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of China
Tel +86-571-8663-3377
Email [email protected]

Objective: To investigate the potential causal associations of circulating levels of growth differentiation factor 15 (GDF-15) with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) using a Mendelian randomization (MR) design.
Methods: A genome-wide association study (GWAS) of GDF-15 among 5,440 individuals of European ancestry was used to identify genetic instruments. Summary statistics of SLE, RA and IBD were obtained from publicly available GWASs. We conducted an MR study using the inverse-variance weighted (IVW) method, supplemented with simple-median and weighted-median methods. Cochran Q test and MR-Egger regression were used to detect potential heterogeneity and directional pleiotropy. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.
Results: We found that genetically predicted high circulating GDF-15 levels were associated with a decreased risk of SLE (OR 0.80, 95% CI 0.68– 0.92 by IVW), with similar results in sensitivity analyses. In replication analysis using summary data from another SLE GWAS, the results were consistent (OR 0.82, 95% CI 0.71– 0.93 by IVW). Moreover, no evidence of heterogeneity or pleiotropy was detected. However, genetically determined circulating levels of GDF-15 were not associated with risk of RA or IBD in the primary analysis and subsequent sensitivity analyses.
Conclusions: Our study suggested an inverse association between circulating GDF-15 levels and risk of SLE, and further studies are warranted to elucidate the underlying biological mechanisms. There was limited evidence supporting a causal association of circulating GDF-15 levels with risk of RA and IBD.

Keywords: growth differentiation factor 15, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Mendelian randomization, single nucleotide polymorphism

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