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- Title
Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function.
- Authors
Cho, Jeong Min; Koh, Jung Hun; Kim, Seong Geun; Lee, Soojin; Kim, Yaerim; Cho, Semin; Kim, Kwangsoo; Kim, Yong Chul; Han, Seung Seok; Lee, Hajeong; Lee, Jung Pyo; Joo, Kwon Wook; Lim, Chun Soo; Kim, Yon Su; Kim, Dong Ki; Park, Sehoon
- Abstract
Interleukins (ILs), key cytokine family of inflammatory response, are closely associated with kidney function. However, the causal effect of various ILs on kidney function needs further investigation. Here we show two-sample summary-level Mendelian randomization (MR) analysis that examined the causality between serum IL levels and kidney function. Genetic variants with strong association with serum IL levels were obtained from a previous genome-wide association study meta-analysis. Summary-level data for estimated glomerular filtration rate (eGFR) were obtained from CKDGen database. As a main MR analysis, multiplicative random-effects inverse-variance weighted method was performed. Pleiotropy-robust MR analysis, including MR-Egger with bootstrapped error and weighted median methods, were also implemented. We tested the causal estimates from nine ILs on eGFR traits. Among the results, higher genetically predicted serum IL-1 receptor antagonist level was significantly associated with higher eGFR values in the meta-analysis of CKDGen and the UK Biobank data. In addition, the result was consistent towards eGFR decline phenotype of the outcome database. Otherwise, nonsignificant association was identified between other genetically predicted ILs and eGFR outcome. These findings support the clinical importance of IL-1 receptor antagonist-associated pathway in relation to kidney function in the general individuals, particularly highlighting the importance of IL-1 receptor antagonist. Mendelian randomization analysis reveals that higher genetically predicted serum IL-1 receptor antagonist levels are associated with preserved kidney function (higher estimated glomerular filtration rate) in the meta-analysis of CKDGen and the UK Biobank data.
- Subjects
UNITED Kingdom; KIDNEY physiology; GENOME-wide association studies; GLOMERULAR filtration rate; INTERLEUKIN-1; INTERLEUKINS
- Publication
Communications Biology, 2023, Vol 6, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-023-05091-8