Genetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization Study

Background: Positive associations between inflammatory biomarkers and the risk of heart failure (HF) have been reported in conventional observational studies. However, the causal effects of inflammatory biomarkers on HF have not been fully elucidated. We conducted a Mendelian randomization (MR) stud...

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Autores principales:	Xintao Li, Shi Peng, Bo Guan, Songwen Chen, Genqing Zhou, Yong Wei, Chao Gong, Juan Xu, Xiaofeng Lu, Xiaoyu Zhang, Shaowen Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	heart failure Mendelian randomization C-reactive protein fibrinogen interleukin Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/93a5a3a74b6947c583aaa09bad956236
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spelling	oai:doaj.org-article:93a5a3a74b6947c583aaa09bad9562362021-11-22T06:20:12ZGenetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization Study2297-055X10.3389/fcvm.2021.734400https://doaj.org/article/93a5a3a74b6947c583aaa09bad9562362021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.734400/fullhttps://doaj.org/toc/2297-055XBackground: Positive associations between inflammatory biomarkers and the risk of heart failure (HF) have been reported in conventional observational studies. However, the causal effects of inflammatory biomarkers on HF have not been fully elucidated. We conducted a Mendelian randomization (MR) study to examine the possible etiological roles of inflammatory biomarkers in HF.Methods: Summary statistical data for the associations between single nucleotide polymorphisms (SNPs) and C-reactive protein (CRP), fibrinogen, and components of the interleukin-1 (IL-1)-interleukin-6 (IL-6) inflammatory signaling pathway, namely, interleukin-1β (IL-1β), IL-1 receptor antagonist (IL-1ra), IL-6, and soluble IL-6 receptor (sIL-6r), were obtained from genome-wide association studies (GWASs) for individuals of European descent. The GWAS dataset of 977,323 participants of European ancestry, which included 47,309 HF cases and 930,014 controls, was collected to identify genetic variants underlying HF. A two-sample Mendelian randomization framework was implemented to examine the causality of the association between these inflammatory biomarkers and HF.Results: Our MR analyses found that genetically determined CRP and fibrinogen were not causally associated with HF risk (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.84–1.02, p = 0.15; OR = 0.94, 95% CI = 0.55–1.58, p = 0.80, respectively). These findings remained consistent using different Mendelian randomization methods and in sensitivity analyses. For the IL-1-IL-6 pathway, causal estimates for IL-6 (OR = 0.86, 95% CI 0.81–0.91, p < 0.001), but not for IL-1β, IL-1ra, or sIL-6r, were significant. However, the association between genetically determined IL-6 and HF risk became non-significant after excluding SNPs with potential pleiotropy (OR = 0.89, 95% CI = 0.77–1.03, p = 0.12).Conclusion: Our study did not identify convincing evidence to support that CRP and fibrinogen, together with their upstream IL-1-IL-6 signaling pathway, were causally associated with HF risk.Xintao LiShi PengBo GuanSongwen ChenGenqing ZhouYong WeiChao GongJuan XuXiaofeng LuXiaoyu ZhangXiaoyu ZhangShaowen LiuFrontiers Media S.A.articleheart failureMendelian randomizationC-reactive proteinfibrinogeninterleukinDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	heart failure Mendelian randomization C-reactive protein fibrinogen interleukin Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	heart failure Mendelian randomization C-reactive protein fibrinogen interleukin Diseases of the circulatory (Cardiovascular) system RC666-701 Xintao Li Shi Peng Bo Guan Songwen Chen Genqing Zhou Yong Wei Chao Gong Juan Xu Xiaofeng Lu Xiaoyu Zhang Xiaoyu Zhang Shaowen Liu Genetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization Study
description	Background: Positive associations between inflammatory biomarkers and the risk of heart failure (HF) have been reported in conventional observational studies. However, the causal effects of inflammatory biomarkers on HF have not been fully elucidated. We conducted a Mendelian randomization (MR) study to examine the possible etiological roles of inflammatory biomarkers in HF.Methods: Summary statistical data for the associations between single nucleotide polymorphisms (SNPs) and C-reactive protein (CRP), fibrinogen, and components of the interleukin-1 (IL-1)-interleukin-6 (IL-6) inflammatory signaling pathway, namely, interleukin-1β (IL-1β), IL-1 receptor antagonist (IL-1ra), IL-6, and soluble IL-6 receptor (sIL-6r), were obtained from genome-wide association studies (GWASs) for individuals of European descent. The GWAS dataset of 977,323 participants of European ancestry, which included 47,309 HF cases and 930,014 controls, was collected to identify genetic variants underlying HF. A two-sample Mendelian randomization framework was implemented to examine the causality of the association between these inflammatory biomarkers and HF.Results: Our MR analyses found that genetically determined CRP and fibrinogen were not causally associated with HF risk (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.84–1.02, p = 0.15; OR = 0.94, 95% CI = 0.55–1.58, p = 0.80, respectively). These findings remained consistent using different Mendelian randomization methods and in sensitivity analyses. For the IL-1-IL-6 pathway, causal estimates for IL-6 (OR = 0.86, 95% CI 0.81–0.91, p < 0.001), but not for IL-1β, IL-1ra, or sIL-6r, were significant. However, the association between genetically determined IL-6 and HF risk became non-significant after excluding SNPs with potential pleiotropy (OR = 0.89, 95% CI = 0.77–1.03, p = 0.12).Conclusion: Our study did not identify convincing evidence to support that CRP and fibrinogen, together with their upstream IL-1-IL-6 signaling pathway, were causally associated with HF risk.
format	article
author	Xintao Li Shi Peng Bo Guan Songwen Chen Genqing Zhou Yong Wei Chao Gong Juan Xu Xiaofeng Lu Xiaoyu Zhang Xiaoyu Zhang Shaowen Liu
author_facet	Xintao Li Shi Peng Bo Guan Songwen Chen Genqing Zhou Yong Wei Chao Gong Juan Xu Xiaofeng Lu Xiaoyu Zhang Xiaoyu Zhang Shaowen Liu
author_sort	Xintao Li
title	Genetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization Study
title_short	Genetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization Study
title_full	Genetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization Study
title_fullStr	Genetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization Study
title_full_unstemmed	Genetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization Study
title_sort	genetically determined inflammatory biomarkers and the risk of heart failure: a mendelian randomization study
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/93a5a3a74b6947c583aaa09bad956236
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Genetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization Study

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