Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization study
BackgroundObservational studies have shown that calcific aortic valve stenosis (CAVS) is associated with a shorter telomere length (TL). However, the results of observational studies are often influenced by confounding factors and reverse causal associations; it is unclear whether there is a causal...
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1077686/full |
| _version_ | 1811298946975268864 |
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| author | Junkui Wang Junkui Wang Yan Hao Zhanfang Zhu Bo Liu Xuejun Zhang Na Wei Ting Wang Ying Lv Cuixiang Xu Meijuan Ma Yulian Zhang Yulian Zhang Fuqiang Liu Fuqiang Liu |
| author_facet | Junkui Wang Junkui Wang Yan Hao Zhanfang Zhu Bo Liu Xuejun Zhang Na Wei Ting Wang Ying Lv Cuixiang Xu Meijuan Ma Yulian Zhang Yulian Zhang Fuqiang Liu Fuqiang Liu |
| author_sort | Junkui Wang |
| collection | DOAJ |
| description | BackgroundObservational studies have shown that calcific aortic valve stenosis (CAVS) is associated with a shorter telomere length (TL). However, the results of observational studies are often influenced by confounding factors and reverse causal associations; it is unclear whether there is a causal relationship between TL and CAVS. This study aimed to investigate the causal relationship between TL and CAVS.Materials and methodsGenome-wide association study (GWAS) data on TL (n = 472,174) and CAVS (n = 311,437) were used to assess the effect of TL on CAVS. All the participants were of European ancestry. Three Mendelian randomization (MR) methods, namely, MR-Egger, weighted median, and inverse variance weighted (IVW), were used to assess the potential causal effect of TL on CAVS. Heterogeneity was assessed using Cochran’s Q statistic. Leave-one-out and MR-Egger regression methods were used for sensitivity and pleiotropy analyses. Forward and reverse MR analyses were performed.ResultsIn total, 118 valid and independent TL genetic instrumental variants were extracted from the GWAS dataset. MR analysis showed that TL was negatively associated with CAVS (odds ratios [OR] = 0.727, 95% confidence interval [CI]: 0.565–0.936, and P = 0.013 by weighted median; OR = 0.763, 95% CI: 0.634–0.920, and P = 0.005 by IVW; OR = 0.757, 95% CI: 0.549–1.044, and P = 0.055 by MR-Egger). Sensitivity and pleiotropy analyses showed that the results of this study were relatively stable and that there was no significant pleiotropy. Reverse MR analyses consistently suggested the absence of causal effects of CAVS liability on TL levels.ConclusionA causal relationship between the shortening of TL and the development of CAVS in the European population was suggested in this study, and a theoretical basis was provided to investigate the pathogenesis of CAVS. |
| first_indexed | 2024-04-13T06:27:51Z |
| format | Article |
| id | doaj.art-ede9a8800e2a4e49ab9a624f204d25a4 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-13T06:27:51Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-ede9a8800e2a4e49ab9a624f204d25a42022-12-22T02:58:21ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-12-01910.3389/fmed.2022.10776861077686Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization studyJunkui Wang0Junkui Wang1Yan Hao2Zhanfang Zhu3Bo Liu4Xuejun Zhang5Na Wei6Ting Wang7Ying Lv8Cuixiang Xu9Meijuan Ma10Yulian Zhang11Yulian Zhang12Fuqiang Liu13Fuqiang Liu14Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, ChinaShaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, ChinaXi’an Jiaotong University Hospital, Xi’an, ChinaXi’an Jiaotong University Hospital, Xi’an, ChinaDepartment of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, ChinaDepartment of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, ChinaDepartment of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, ChinaDepartment of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, ChinaDepartment of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, ChinaShaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, ChinaDepartment of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, ChinaShaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, ChinaDepartment of Nursing, Shaanxi Provincial People’s Hospital, Xi’an, ChinaDepartment of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, ChinaShaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, ChinaBackgroundObservational studies have shown that calcific aortic valve stenosis (CAVS) is associated with a shorter telomere length (TL). However, the results of observational studies are often influenced by confounding factors and reverse causal associations; it is unclear whether there is a causal relationship between TL and CAVS. This study aimed to investigate the causal relationship between TL and CAVS.Materials and methodsGenome-wide association study (GWAS) data on TL (n = 472,174) and CAVS (n = 311,437) were used to assess the effect of TL on CAVS. All the participants were of European ancestry. Three Mendelian randomization (MR) methods, namely, MR-Egger, weighted median, and inverse variance weighted (IVW), were used to assess the potential causal effect of TL on CAVS. Heterogeneity was assessed using Cochran’s Q statistic. Leave-one-out and MR-Egger regression methods were used for sensitivity and pleiotropy analyses. Forward and reverse MR analyses were performed.ResultsIn total, 118 valid and independent TL genetic instrumental variants were extracted from the GWAS dataset. MR analysis showed that TL was negatively associated with CAVS (odds ratios [OR] = 0.727, 95% confidence interval [CI]: 0.565–0.936, and P = 0.013 by weighted median; OR = 0.763, 95% CI: 0.634–0.920, and P = 0.005 by IVW; OR = 0.757, 95% CI: 0.549–1.044, and P = 0.055 by MR-Egger). Sensitivity and pleiotropy analyses showed that the results of this study were relatively stable and that there was no significant pleiotropy. Reverse MR analyses consistently suggested the absence of causal effects of CAVS liability on TL levels.ConclusionA causal relationship between the shortening of TL and the development of CAVS in the European population was suggested in this study, and a theoretical basis was provided to investigate the pathogenesis of CAVS.https://www.frontiersin.org/articles/10.3389/fmed.2022.1077686/fulltelomere lengthcalcific aortic valve stenosisgenome-wide association studyMendelian randomizationsingle nucleotide polymorphism |
| spellingShingle | Junkui Wang Junkui Wang Yan Hao Zhanfang Zhu Bo Liu Xuejun Zhang Na Wei Ting Wang Ying Lv Cuixiang Xu Meijuan Ma Yulian Zhang Yulian Zhang Fuqiang Liu Fuqiang Liu Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization study Frontiers in Medicine telomere length calcific aortic valve stenosis genome-wide association study Mendelian randomization single nucleotide polymorphism |
| title | Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization study |
| title_full | Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization study |
| title_fullStr | Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization study |
| title_full_unstemmed | Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization study |
| title_short | Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization study |
| title_sort | causality of telomere length associated with calcific aortic valvular stenosis a mendelian randomization study |
| topic | telomere length calcific aortic valve stenosis genome-wide association study Mendelian randomization single nucleotide polymorphism |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1077686/full |
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