000 03429 am a22003613u 4500
042 _adc
100 1 0 _aDonovan, Killian
_eauthor
_93106
700 1 0 _aHerrington, William G.
_eauthor
_92196
700 1 0 _aParé, Guillaume
_eauthor
_93107
700 1 0 _aPigeyre, Marie
_eauthor
_93108
700 1 0 _aHaynes, Richard
_eauthor
_92234
700 1 0 _aSardell, Rebecca
_eauthor
_93109
700 1 0 _aButterworth, Adam S.
_eauthor
_93110
700 1 0 _aFolkersen, Lasse
_eauthor
_93111
700 1 0 _aGustafsson, Stefan
_eauthor
_93112
700 1 0 _aWang, Qin
_eauthor
_93113
700 1 0 _aBaigent, Colin
_eauthor
_92233
700 1 0 _aMälarstig, Anders
_eauthor
_93114
700 1 0 _aHolmes, Michael V.
_eauthor
_93115
700 1 0 _aStaplin, Natalie
_eauthor
_92197
245 0 0 _aFibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: a Mendelian Randomization study
260 _c2023-01-01.
500 _a/pmc/articles/PMC7614195/
500 _a/pubmed/36719157
520 _aBACKGROUND: 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.
540 _a
540 _ahttps://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/)
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nClin J Am Soc Nephrol
856 4 1 _uhttp://dx.doi.org/10.2215/CJN.05080422
_zConnect to this object online.
999 _c1003
_d1003