| Title: | Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases |
| Journal: | Clinical Journal of the American Society of Nephrology |
| Published: | 1 Jan 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36719157/ |
| DOI: | https://doi.org/10.2215/cjn.05080422 |
| URL: | http://uu.diva-portal.org/smash/get/diva2:1745425/FULLTEXT01 |
Publication 10896
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Abstract
BACKGROUND: Fibroblast growth factor-23 (FGF-23) is associated with a range of cardiovascular and noncardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.</p>
METHODS: SCALLOP Consortium data of 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), nonatherosclerotic cardiovascular disease (n=12,652), and noncardiovascular 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>
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 noncardiovascular outcomes. In UK Biobank, the odds ratio (OR) for any atherosclerotic cardiovascular disease per 1-SD higher genetically predicted logFGF-23 was 1.03 (95% confidence interval [95% CI], 0.98 to 1.08), and for any nonatherosclerotic cardiovascular disease, it was 1.01 (95% CI, 0.94 to 1.09). The ORs in the case-control consortia were 1.00 (95% CI, 0.97 to 1.03) for coronary artery disease, 1.01 (95% CI, 0.95 to 1.07) for stroke, and 1.00 (95% CI, 0.95 to 1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalities.</p>
CONCLUSIONS: Genetically predicted FGF-23 levels are not associated with atherosclerotic and nonatherosclerotic cardiovascular diseases, suggesting no important causal link.</p>
PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_01_10_CJN05080422.mp3.</p>
14 Authors
- Killian Donovan
- William G. Herrington
- Guillaume Paré
- Marie Pigeyre
- Richard Haynes
- Rebecca Sardell
- Adam S. Butterworth
- Lasse Folkersen
- Stefan Gustafsson
- Qin Wang
- Colin Baigent
- Anders Mälarstig
- Michael V. Holmes
- Natalie Staplin
1 Application
| Application ID | Title |
|---|---|
| 15595 | Renal Studies Group and Population Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health (NDPH), University of Oxford |
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