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Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study
BACKGROUND: While targeted systemic inflammatory modulators show promise in preventing chronic kidney disease (CKD) progression, the causal link between specific inflammatory factors and CKD remains uncertain. METHODS: Using a genome-wide association study of 41 serum cytokines from 8,293 Finnish in...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498994/ https://www.ncbi.nlm.nih.gov/pubmed/37711613 http://dx.doi.org/10.3389/fimmu.2023.1229636 |
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author | Li, Hongdian Li, Mingxuan Liu, Cong He, Pengfei Dong, Ao Dong, Shaoning Zhang, Mianzhi |
author_facet | Li, Hongdian Li, Mingxuan Liu, Cong He, Pengfei Dong, Ao Dong, Shaoning Zhang, Mianzhi |
author_sort | Li, Hongdian |
collection | PubMed |
description | BACKGROUND: While targeted systemic inflammatory modulators show promise in preventing chronic kidney disease (CKD) progression, the causal link between specific inflammatory factors and CKD remains uncertain. METHODS: Using a genome-wide association study of 41 serum cytokines from 8,293 Finnish individuals, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. In addition, we genetically predicted causal associations between inflammatory factors and 5 phenotypes, including CKD, estimated glomerular filtration rate (eGFR), dialysis, rapid progression of CKD, and rapid decline in eGFR. Inverse variance weighting (IVW) served as the primary MR method, while MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were utilized for sensitivity analysis. Cochrane’s Q test for heterogeneity. Leave-one-out method ensured stability of MR results, and Bonferroni correction assessed causal relationship strength. RESULTS: Seventeen cytokines were associated with diverse renal outcomes. Among them, after Bonferroni correction test, higher tumor necrosis factor alpha levels were associated with a rapid decrease in eGFR (OR = 1.064, 95% CI 1.028 – 1.103, P = 0.001), higher interleukin-4 levels were associated with an increase in eGFR (β = 0.003, 95% CI 0.001 – 0.005, P = 0.002), and higher growth regulated oncogene alpha (GROα) levels were associated with an increased risk of CKD (OR=1.035, 95% CI 1.012 - 1.058, P = 0.003). In contrast, genetic susceptibility to CKD was associated with an increase in GROa, and a decrease in eGFR may lead to an increase in stem cell factor. We did not find the presence of horizontal pleiotropy during the analysis. CONCLUSION: We discovered causally related inflammatory factors that contribute to the initiation and progression of CKD at the genetic prediction level. |
format | Online Article Text |
id | pubmed-10498994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104989942023-09-14 Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study Li, Hongdian Li, Mingxuan Liu, Cong He, Pengfei Dong, Ao Dong, Shaoning Zhang, Mianzhi Front Immunol Immunology BACKGROUND: While targeted systemic inflammatory modulators show promise in preventing chronic kidney disease (CKD) progression, the causal link between specific inflammatory factors and CKD remains uncertain. METHODS: Using a genome-wide association study of 41 serum cytokines from 8,293 Finnish individuals, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. In addition, we genetically predicted causal associations between inflammatory factors and 5 phenotypes, including CKD, estimated glomerular filtration rate (eGFR), dialysis, rapid progression of CKD, and rapid decline in eGFR. Inverse variance weighting (IVW) served as the primary MR method, while MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were utilized for sensitivity analysis. Cochrane’s Q test for heterogeneity. Leave-one-out method ensured stability of MR results, and Bonferroni correction assessed causal relationship strength. RESULTS: Seventeen cytokines were associated with diverse renal outcomes. Among them, after Bonferroni correction test, higher tumor necrosis factor alpha levels were associated with a rapid decrease in eGFR (OR = 1.064, 95% CI 1.028 – 1.103, P = 0.001), higher interleukin-4 levels were associated with an increase in eGFR (β = 0.003, 95% CI 0.001 – 0.005, P = 0.002), and higher growth regulated oncogene alpha (GROα) levels were associated with an increased risk of CKD (OR=1.035, 95% CI 1.012 - 1.058, P = 0.003). In contrast, genetic susceptibility to CKD was associated with an increase in GROa, and a decrease in eGFR may lead to an increase in stem cell factor. We did not find the presence of horizontal pleiotropy during the analysis. CONCLUSION: We discovered causally related inflammatory factors that contribute to the initiation and progression of CKD at the genetic prediction level. Frontiers Media S.A. 2023-08-30 /pmc/articles/PMC10498994/ /pubmed/37711613 http://dx.doi.org/10.3389/fimmu.2023.1229636 Text en Copyright © 2023 Li, Li, Liu, He, Dong, Dong and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Li, Hongdian Li, Mingxuan Liu, Cong He, Pengfei Dong, Ao Dong, Shaoning Zhang, Mianzhi Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study |
title | Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study |
title_full | Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study |
title_fullStr | Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study |
title_full_unstemmed | Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study |
title_short | Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study |
title_sort | causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional mendelian randomization study |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498994/ https://www.ncbi.nlm.nih.gov/pubmed/37711613 http://dx.doi.org/10.3389/fimmu.2023.1229636 |
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