TY  - BOOK
AU  - Donovan,Killian
AU  - Herrington,William G.
AU  - Paré,Guillaume
AU  - Pigeyre,Marie
AU  - Haynes,Richard
AU  - Sardell,Rebecca
AU  - Butterworth,Adam S.
AU  - Folkersen,Lasse
AU  - Gustafsson,Stefan
AU  - Wang,Qin
AU  - Baigent,Colin
AU  - Mälarstig,Anders
AU  - Holmes,Michael V.
AU  - Staplin,Natalie
TI  - Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: a Mendelian Randomization study
PY  - 2023///-01-01
KW  - Text
KW  - local
N1  - /pmc/articles/PMC7614195; /pubmed/36719157
N2  - 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
UR  - http://dx.doi.org/10.2215/CJN.05080422
ER  -