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Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function

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 causa...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349143/
https://www.ncbi.nlm.nih.gov/pubmed/37452175
http://dx.doi.org/10.1038/s42003-023-05091-8
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author 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
author_facet 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
author_sort Cho, Jeong Min
collection PubMed
description 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.
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spelling pubmed-103491432023-07-16 Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function 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 Commun Biol Article 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. Nature Publishing Group UK 2023-07-14 /pmc/articles/PMC10349143/ /pubmed/37452175 http://dx.doi.org/10.1038/s42003-023-05091-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function
title Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function
title_full Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function
title_fullStr Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function
title_full_unstemmed Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function
title_short Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function
title_sort mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349143/
https://www.ncbi.nlm.nih.gov/pubmed/37452175
http://dx.doi.org/10.1038/s42003-023-05091-8
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