Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study
BackgroundSeveral studies have reported a protective role of circulating α-Klotho on cardiovascular diseases (CVD); however, the causality remains unclear. We aim to elucidate whether genetically predicted circulating α-Klotho levels were causally associated with the risk of coronary artery disease...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.842846/full |
| _version_ | 1828750818131574784 |
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| author | Xingang Sun Lu Chen Yuxian He Liangrong Zheng |
| author_facet | Xingang Sun Lu Chen Yuxian He Liangrong Zheng |
| author_sort | Xingang Sun |
| collection | DOAJ |
| description | BackgroundSeveral studies have reported a protective role of circulating α-Klotho on cardiovascular diseases (CVD); however, the causality remains unclear. We aim to elucidate whether genetically predicted circulating α-Klotho levels were causally associated with the risk of coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes.MethodsA two-sample Mendelian randomization (MR) study was designed, with 5 single-nucleotide polymorphisms associated with circulating α-Klotho levels utilized as instrumental variables. MR estimates on each CVD outcome derived from the fixed-effects inverse-variance weighted (IVW) approach in different data sources were combined by the fixed-effects meta-analysis approach, complemented by several sensitivity analyses including the simple median, the weighed median, MR-Egger regression, and MR-pleiotropy residual sum and outlier.ResultsIn the meta-analysis combining different data sources, suggestive inverse causal association of circulating α-Klotho concentrations with CAD [Odds ratio (OR), 0.97; 95% confidence interval (CI), 0.94, 1.00; P = 0.044] and significant inverse association of circulating α-Klotho concentrations with AF (OR, 0.96; 95% CI, 0.93, 0.99; P = 0.005) was observed. However, there was no causal association of α-Klotho with HF, any stroke, IS, or IS subtypes neither in different data sources nor in the meta-analysis. Complementary sensitivity analyses showed consistent and robust results in general.ConclusionEvidence was found for a protective effect of circulating α-Klotho on the prevention of AF risk. However, no significant causal association between genetically predicted circulating α-Klotho levels and risk of CAD, HF, stroke, IS, or IS subtypes was found. |
| first_indexed | 2024-12-10T20:45:06Z |
| format | Article |
| id | doaj.art-55b6cde463c54181b61be5edefed8175 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-10T20:45:06Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-55b6cde463c54181b61be5edefed81752022-12-22T01:34:16ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-02-011310.3389/fendo.2022.842846842846Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization StudyXingang SunLu ChenYuxian HeLiangrong ZhengBackgroundSeveral studies have reported a protective role of circulating α-Klotho on cardiovascular diseases (CVD); however, the causality remains unclear. We aim to elucidate whether genetically predicted circulating α-Klotho levels were causally associated with the risk of coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes.MethodsA two-sample Mendelian randomization (MR) study was designed, with 5 single-nucleotide polymorphisms associated with circulating α-Klotho levels utilized as instrumental variables. MR estimates on each CVD outcome derived from the fixed-effects inverse-variance weighted (IVW) approach in different data sources were combined by the fixed-effects meta-analysis approach, complemented by several sensitivity analyses including the simple median, the weighed median, MR-Egger regression, and MR-pleiotropy residual sum and outlier.ResultsIn the meta-analysis combining different data sources, suggestive inverse causal association of circulating α-Klotho concentrations with CAD [Odds ratio (OR), 0.97; 95% confidence interval (CI), 0.94, 1.00; P = 0.044] and significant inverse association of circulating α-Klotho concentrations with AF (OR, 0.96; 95% CI, 0.93, 0.99; P = 0.005) was observed. However, there was no causal association of α-Klotho with HF, any stroke, IS, or IS subtypes neither in different data sources nor in the meta-analysis. Complementary sensitivity analyses showed consistent and robust results in general.ConclusionEvidence was found for a protective effect of circulating α-Klotho on the prevention of AF risk. However, no significant causal association between genetically predicted circulating α-Klotho levels and risk of CAD, HF, stroke, IS, or IS subtypes was found.https://www.frontiersin.org/articles/10.3389/fendo.2022.842846/fullα-klothocoronary artery diseasemyocardial infarctionatrial fibrillationheart failurestroke |
| spellingShingle | Xingang Sun Lu Chen Yuxian He Liangrong Zheng Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study Frontiers in Endocrinology α-klotho coronary artery disease myocardial infarction atrial fibrillation heart failure stroke |
| title | Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study |
| title_full | Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study |
| title_fullStr | Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study |
| title_full_unstemmed | Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study |
| title_short | Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study |
| title_sort | circulating α klotho levels in relation to cardiovascular diseases a mendelian randomization study |
| topic | α-klotho coronary artery disease myocardial infarction atrial fibrillation heart failure stroke |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.842846/full |
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