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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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.734400/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T23:33:57Z |
| format | Article |
| id | doaj.art-93a5a3a74b6947c583aaa09bad956236 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-18T23:33:57Z |
| publishDate | 2021-11-01 |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-93a5a3a74b6947c583aaa09bad9562362022-12-21T20:47:37ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-11-01810.3389/fcvm.2021.734400734400Genetically Determined Inflammatory Biomarkers and the Risk of Heart Failure: A Mendelian Randomization StudyXintao Li0Shi Peng1Bo Guan2Songwen Chen3Genqing Zhou4Yong Wei5Chao Gong6Juan Xu7Xiaofeng Lu8Xiaoyu Zhang9Xiaoyu Zhang10Shaowen Liu11Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaGeriatric Cardiology Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBeijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, ChinaDepartment of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fcvm.2021.734400/fullheart failureMendelian randomizationC-reactive proteinfibrinogeninterleukin |
| spellingShingle | 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 Frontiers in Cardiovascular Medicine heart failure Mendelian randomization C-reactive protein fibrinogen interleukin |
| title | 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_short | 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 |
| topic | heart failure Mendelian randomization C-reactive protein fibrinogen interleukin |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.734400/full |
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