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Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study

Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study. Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We...

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Autores principales: Liu, Meiling, Luo, Ping, Liu, Lihua, Wei, Xianping, Bai, Xue, Li, Jicui, Wu, Linlin, Luo, Manyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150136/
https://www.ncbi.nlm.nih.gov/pubmed/37139230
http://dx.doi.org/10.3389/fgene.2023.1129247
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author Liu, Meiling
Luo, Ping
Liu, Lihua
Wei, Xianping
Bai, Xue
Li, Jicui
Wu, Linlin
Luo, Manyu
author_facet Liu, Meiling
Luo, Ping
Liu, Lihua
Wei, Xianping
Bai, Xue
Li, Jicui
Wu, Linlin
Luo, Manyu
author_sort Liu, Meiling
collection PubMed
description Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study. Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn’s disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran’s Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction. Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66–0.89, and p = 3.66 × 10(−4)), SS (OR: 0.75, CI: 0.58–0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68–0.88, and p = 9.85 × 10(−5)), hypothyroidism (OR: 0.84, 95% CI: 0.78–0.91, and p = 7,08 × 10(−6)), hyperthyroidism (OR: 0.60, 95% CI: 0.44–0.83, and p = 1.90 × 10(−3)), sarcoidosis (OR: 0.67, 95% CI: 0.54–0.83, and p = 2.60 × 10(−4)), and IPF (OR: 0.41, 95% CI: 0.29–0.58, and p = 4.11 × 10(−7)) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18–1.94, and p = 9.66 × 10(−4)). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62–1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37–2.54, and p = 8.01 × 10(−5)). Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs.
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spelling pubmed-101501362023-05-02 Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study Liu, Meiling Luo, Ping Liu, Lihua Wei, Xianping Bai, Xue Li, Jicui Wu, Linlin Luo, Manyu Front Genet Genetics Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study. Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn’s disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran’s Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction. Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66–0.89, and p = 3.66 × 10(−4)), SS (OR: 0.75, CI: 0.58–0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68–0.88, and p = 9.85 × 10(−5)), hypothyroidism (OR: 0.84, 95% CI: 0.78–0.91, and p = 7,08 × 10(−6)), hyperthyroidism (OR: 0.60, 95% CI: 0.44–0.83, and p = 1.90 × 10(−3)), sarcoidosis (OR: 0.67, 95% CI: 0.54–0.83, and p = 2.60 × 10(−4)), and IPF (OR: 0.41, 95% CI: 0.29–0.58, and p = 4.11 × 10(−7)) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18–1.94, and p = 9.66 × 10(−4)). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62–1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37–2.54, and p = 8.01 × 10(−5)). Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs. Frontiers Media S.A. 2023-04-17 /pmc/articles/PMC10150136/ /pubmed/37139230 http://dx.doi.org/10.3389/fgene.2023.1129247 Text en Copyright © 2023 Liu, Luo, Liu, Wei, Bai, Li, Wu and Luo. 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 Genetics
Liu, Meiling
Luo, Ping
Liu, Lihua
Wei, Xianping
Bai, Xue
Li, Jicui
Wu, Linlin
Luo, Manyu
Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study
title Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study
title_full Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study
title_fullStr Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study
title_full_unstemmed Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study
title_short Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study
title_sort immune-mediated inflammatory diseases and leukocyte telomere length: a mendelian randomization study
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150136/
https://www.ncbi.nlm.nih.gov/pubmed/37139230
http://dx.doi.org/10.3389/fgene.2023.1129247
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