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Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: a Mendelian Randomization study

BACKGROUND: 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. METHODS: SC...

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Autores principales: Donovan, Killian, Herrington, William G., Paré, Guillaume, Pigeyre, Marie, Haynes, Richard, Sardell, Rebecca, Butterworth, Adam S., Folkersen, Lasse, Gustafsson, Stefan, Wang, Qin, Baigent, Colin, Mälarstig, Anders, Holmes, Michael V., Staplin, Natalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614195/
https://www.ncbi.nlm.nih.gov/pubmed/36719157
http://dx.doi.org/10.2215/CJN.05080422
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author Donovan, Killian
Herrington, William G.
Paré, Guillaume
Pigeyre, Marie
Haynes, Richard
Sardell, Rebecca
Butterworth, Adam S.
Folkersen, Lasse
Gustafsson, Stefan
Wang, Qin
Baigent, Colin
Mälarstig, Anders
Holmes, Michael V.
Staplin, Natalie
author_facet Donovan, Killian
Herrington, William G.
Paré, Guillaume
Pigeyre, Marie
Haynes, Richard
Sardell, Rebecca
Butterworth, Adam S.
Folkersen, Lasse
Gustafsson, Stefan
Wang, Qin
Baigent, Colin
Mälarstig, Anders
Holmes, Michael V.
Staplin, Natalie
author_sort Donovan, Killian
collection PubMed
description BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Genetically predicted FGF-23 levels are not associated atherosclerotic and non-atherosclerotic cardiovascular diseases, suggesting no important causal link.
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spelling pubmed-76141952023-02-17 Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: a Mendelian Randomization study Donovan, Killian Herrington, William G. Paré, Guillaume Pigeyre, Marie Haynes, Richard Sardell, Rebecca Butterworth, Adam S. Folkersen, Lasse Gustafsson, Stefan Wang, Qin Baigent, Colin Mälarstig, Anders Holmes, Michael V. Staplin, Natalie Clin J Am Soc Nephrol Article BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Genetically predicted FGF-23 levels are not associated atherosclerotic and non-atherosclerotic cardiovascular diseases, suggesting no important causal link. 2023-01-01 /pmc/articles/PMC7614195/ /pubmed/36719157 http://dx.doi.org/10.2215/CJN.05080422 Text en https://creativecommons.org/licenses/by/4.0/Open Access For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Article
Donovan, Killian
Herrington, William G.
Paré, Guillaume
Pigeyre, Marie
Haynes, Richard
Sardell, Rebecca
Butterworth, Adam S.
Folkersen, Lasse
Gustafsson, Stefan
Wang, Qin
Baigent, Colin
Mälarstig, Anders
Holmes, Michael V.
Staplin, Natalie
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614195/
https://www.ncbi.nlm.nih.gov/pubmed/36719157
http://dx.doi.org/10.2215/CJN.05080422
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