Fibroblast growth factor-23 and risk of cardiovascular diseases: a Mendelian randomization study
<p><strong>Background:</strong> Fibroblast growth factor 23 (FGF-23) is associated with a range of cardiovascular and non-cardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help con...
| Main Authors: | , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
American Society of Nephrology
2022
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| _version_ | 1826309314709553152 |
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| author | Donovan, K Herrington, W Haynes, R Sardell, R Baigent, C Holmes, M Staplin, N |
| author_facet | Donovan, K Herrington, W Haynes, R Sardell, R Baigent, C Holmes, M Staplin, N |
| author_sort | Donovan, K |
| collection | OXFORD |
| description | <p><strong>Background:</strong> Fibroblast growth factor 23 (FGF-23) is associated with a range of cardiovascular and non-cardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.</p>
<p><strong>Methods:</strong> SCALLOP consortium data on 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically-predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), of any non-atherosclerotic cardiovascular disease (n=12,652), and of non-cardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309).</p>
<p><strong>Results:</strong> We identified 34 independent variants for circulating FGF-23 which formed a validated genetic score. There were no associations between genetically-predicted FGF-23 and any of the cardiovascular or non-cardiovascular outcomes. In UK Biobank, the odds ratio for any atherosclerotic cardiovascular disease per 1-SD higher genetically-predicted logFGF-23 was 1.03 (95% confidence interval [CI] 0.98-1.08), and for any non-atherosclerotic cardiovascular disease was 1.01 (0.94-1.09). The odds ratios in the case-control consortia were 1.00 (0.97-1.03) for coronary artery disease, 1.01 (0.95-1.07) for stroke, and 1.00 (0.95-1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalties.</p>
<p><strong>Conclusion:</strong> Genetically predicted FGF-23 levels are not associated atherosclerotic and non-atherosclerotic cardiovascular diseases, suggesting no important causal link.</p> |
| first_indexed | 2024-03-07T07:33:49Z |
| format | Journal article |
| id | oxford-uuid:b94e709e-7ffb-499e-90e6-c15cff8f67ce |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:33:49Z |
| publishDate | 2022 |
| publisher | American Society of Nephrology |
| record_format | dspace |
| spelling | oxford-uuid:b94e709e-7ffb-499e-90e6-c15cff8f67ce2023-02-10T10:23:58ZFibroblast growth factor-23 and risk of cardiovascular diseases: a Mendelian randomization studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b94e709e-7ffb-499e-90e6-c15cff8f67ceEnglishSymplectic ElementsAmerican Society of Nephrology2022Donovan, KHerrington, WHaynes, RSardell, RBaigent, CHolmes, MStaplin, N<p><strong>Background:</strong> Fibroblast growth factor 23 (FGF-23) is associated with a range of cardiovascular and non-cardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.</p> <p><strong>Methods:</strong> SCALLOP consortium data on 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically-predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), of any non-atherosclerotic cardiovascular disease (n=12,652), and of non-cardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309).</p> <p><strong>Results:</strong> We identified 34 independent variants for circulating FGF-23 which formed a validated genetic score. There were no associations between genetically-predicted FGF-23 and any of the cardiovascular or non-cardiovascular outcomes. In UK Biobank, the odds ratio for any atherosclerotic cardiovascular disease per 1-SD higher genetically-predicted logFGF-23 was 1.03 (95% confidence interval [CI] 0.98-1.08), and for any non-atherosclerotic cardiovascular disease was 1.01 (0.94-1.09). The odds ratios in the case-control consortia were 1.00 (0.97-1.03) for coronary artery disease, 1.01 (0.95-1.07) for stroke, and 1.00 (0.95-1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalties.</p> <p><strong>Conclusion:</strong> Genetically predicted FGF-23 levels are not associated atherosclerotic and non-atherosclerotic cardiovascular diseases, suggesting no important causal link.</p> |
| spellingShingle | Donovan, K Herrington, W Haynes, R Sardell, R Baigent, C Holmes, M Staplin, N Fibroblast growth factor-23 and risk of cardiovascular diseases: a Mendelian randomization study |
| title | Fibroblast growth factor-23 and risk of cardiovascular diseases: a Mendelian randomization study |
| title_full | Fibroblast growth factor-23 and risk of cardiovascular diseases: a Mendelian randomization study |
| title_fullStr | Fibroblast growth factor-23 and risk of cardiovascular diseases: a Mendelian randomization study |
| title_full_unstemmed | Fibroblast growth factor-23 and risk of cardiovascular diseases: a Mendelian randomization study |
| title_short | Fibroblast growth factor-23 and risk of cardiovascular diseases: a Mendelian randomization study |
| title_sort | fibroblast growth factor 23 and risk of cardiovascular diseases a mendelian randomization study |
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