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The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study

Background: Although observational studies have demonstrated that blood lipids were associated with systemic lupus erythematosus (SLE), the causality of this association remains elusive as traditional observational studies were prone to confounding and reverse causality biases. Here, this study atte...

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Autores principales: Wang, Mingzhu, Huang, Shuo, Lin, Xiaoying, Wen, Chengping, He, Zhixing, Huang, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043646/
https://www.ncbi.nlm.nih.gov/pubmed/35495122
http://dx.doi.org/10.3389/fgene.2022.858653
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author Wang, Mingzhu
Huang, Shuo
Lin, Xiaoying
Wen, Chengping
He, Zhixing
Huang, Lin
author_facet Wang, Mingzhu
Huang, Shuo
Lin, Xiaoying
Wen, Chengping
He, Zhixing
Huang, Lin
author_sort Wang, Mingzhu
collection PubMed
description Background: Although observational studies have demonstrated that blood lipids were associated with systemic lupus erythematosus (SLE), the causality of this association remains elusive as traditional observational studies were prone to confounding and reverse causality biases. Here, this study attempted to reveal the potential causal link between SLE and the levels of four blood lipids (HDL cholesterol, LDL cholesterol, TG, and TC). Methods: Bidirectional two-sample Mendelian randomization (MR) was employed to explore the unconfounded causal associations between the four blood lipids and SLE. In addition, regression-based Multivariate MR (MVMR) to quantify the possible mediation effects of blood lipids on SLE. After a rigorous evaluation of the quality of studies, the single-nucleotide polymorphisms (SNPs) associated with the four blood lipids were selected from the Global Lipids Genetic Consortium (GLGC) consisted of 188,577 individuals of European ancestry, and the SNPs related to SLE were selected from a large-scale genome-wide association study (GWAS) database named IEU GWAS. Subsequently, MR analyses were conducted with inverse-variance weighted (IVW), weighted median, weighted mode, simple mode, and MR-Egger regression. Sensitivity analyses were performed to verify whether heterogeneity and pleiotropy led to bias in the MR results. Results: Bidirectional two-sample MR results demonstrated that there was no significant causal association between SLE and the four blood lipids (When setting SLE as outcome, HDL cholesterol and SLE, IVW OR: 1.32, 95% CI: 1.05∼1.66, p = 1.78E-02; LDL cholesterol and SLE, IVW OR: 1.26, 95% CI: 1.04∼1.53, p = 2.04E-02; TG and SLE, IVW OR: 1.04, 95% CI: 0.71∼1.51, p = 8.44E-01; TC and SLE, IVW OR: 1.07, 95% CI: 0.89∼1.29, p = 4.42E-01; When setting SLE as exposure, SLE and HDL cholesterol, IVW OR: 1.00, 95% CI: 0.99∼1.01, p = 9.51E-01; SLE and LDL cholesterol, IVW OR: 0.99, 95% CI: 0.98∼1.00, p = 3.14E-01; SLE and TG, IVW OR: 0.99, 95% CI: 0.98∼1.00, p = 1.30E-02; SLE and TC, IVW OR: 0.99, 95% CI: 0.98∼1.00, p = 1.56E-01). Our MVMR analysis also provided little evidence that genetically determined lipid traits were significantly associated with the risk of SLE (HDL cholesterol and SLE, p = 9.63E-02; LDL cholesterol and SLE, p = 9.63E-02; TG and SLE, p = 8.44E-01; TC and SLE, p = 4.42E-01). Conclusion: In conclusion, these data provide evidence that genetic changes in lipid traits are not significantly associated with SLE risk in the European population.
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spelling pubmed-90436462022-04-28 The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study Wang, Mingzhu Huang, Shuo Lin, Xiaoying Wen, Chengping He, Zhixing Huang, Lin Front Genet Genetics Background: Although observational studies have demonstrated that blood lipids were associated with systemic lupus erythematosus (SLE), the causality of this association remains elusive as traditional observational studies were prone to confounding and reverse causality biases. Here, this study attempted to reveal the potential causal link between SLE and the levels of four blood lipids (HDL cholesterol, LDL cholesterol, TG, and TC). Methods: Bidirectional two-sample Mendelian randomization (MR) was employed to explore the unconfounded causal associations between the four blood lipids and SLE. In addition, regression-based Multivariate MR (MVMR) to quantify the possible mediation effects of blood lipids on SLE. After a rigorous evaluation of the quality of studies, the single-nucleotide polymorphisms (SNPs) associated with the four blood lipids were selected from the Global Lipids Genetic Consortium (GLGC) consisted of 188,577 individuals of European ancestry, and the SNPs related to SLE were selected from a large-scale genome-wide association study (GWAS) database named IEU GWAS. Subsequently, MR analyses were conducted with inverse-variance weighted (IVW), weighted median, weighted mode, simple mode, and MR-Egger regression. Sensitivity analyses were performed to verify whether heterogeneity and pleiotropy led to bias in the MR results. Results: Bidirectional two-sample MR results demonstrated that there was no significant causal association between SLE and the four blood lipids (When setting SLE as outcome, HDL cholesterol and SLE, IVW OR: 1.32, 95% CI: 1.05∼1.66, p = 1.78E-02; LDL cholesterol and SLE, IVW OR: 1.26, 95% CI: 1.04∼1.53, p = 2.04E-02; TG and SLE, IVW OR: 1.04, 95% CI: 0.71∼1.51, p = 8.44E-01; TC and SLE, IVW OR: 1.07, 95% CI: 0.89∼1.29, p = 4.42E-01; When setting SLE as exposure, SLE and HDL cholesterol, IVW OR: 1.00, 95% CI: 0.99∼1.01, p = 9.51E-01; SLE and LDL cholesterol, IVW OR: 0.99, 95% CI: 0.98∼1.00, p = 3.14E-01; SLE and TG, IVW OR: 0.99, 95% CI: 0.98∼1.00, p = 1.30E-02; SLE and TC, IVW OR: 0.99, 95% CI: 0.98∼1.00, p = 1.56E-01). Our MVMR analysis also provided little evidence that genetically determined lipid traits were significantly associated with the risk of SLE (HDL cholesterol and SLE, p = 9.63E-02; LDL cholesterol and SLE, p = 9.63E-02; TG and SLE, p = 8.44E-01; TC and SLE, p = 4.42E-01). Conclusion: In conclusion, these data provide evidence that genetic changes in lipid traits are not significantly associated with SLE risk in the European population. Frontiers Media S.A. 2022-04-13 /pmc/articles/PMC9043646/ /pubmed/35495122 http://dx.doi.org/10.3389/fgene.2022.858653 Text en Copyright © 2022 Wang, Huang, Lin, Wen, He and Huang. 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
Wang, Mingzhu
Huang, Shuo
Lin, Xiaoying
Wen, Chengping
He, Zhixing
Huang, Lin
The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study
title The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study
title_full The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study
title_fullStr The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study
title_full_unstemmed The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study
title_short The Causal Relationship Between Blood Lipids and Systemic Lupus Erythematosus Risk: A Bidirectional Two-Sample Mendelian Randomization Study
title_sort causal relationship between blood lipids and systemic lupus erythematosus risk: a bidirectional two-sample mendelian randomization study
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043646/
https://www.ncbi.nlm.nih.gov/pubmed/35495122
http://dx.doi.org/10.3389/fgene.2022.858653
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