Association of Genetically Predicted Fibroblast Growth Factor-23 with Heart Failure: A Mendelian Randomization Study.
FGF23
Mendelian randomization analysis
heart failure
human genetics
mineral metabolism
Journal
Clinical journal of the American Society of Nephrology : CJASN
ISSN: 1555-905X
Titre abrégé: Clin J Am Soc Nephrol
Pays: United States
ID NLM: 101271570
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
22
01
2022
accepted:
31
05
2022
pubmed:
29
7
2022
medline:
11
8
2022
entrez:
28
7
2022
Statut:
ppublish
Résumé
Elevated fibroblast growth factor-23 (FGF23) has been consistently associated with heart failure, particularly heart failure with preserved ejection fraction, among patients with CKD and in the general population. FGF23 may directly induce cardiac remodeling and heart failure. However, biases affecting observational studies impede robust causal inferences. Mendelian randomization leverages genetic determinants of a risk factor to examine causality. We performed a two-sample Mendelian randomization to assess causal associations between FGF23 and heart failure. Genetic instruments were genome-wide significant genetic variants associated with FGF23, including variants near Genetically determined FGF23 was not associated with overall heart failure in the Heart Failure Molecular Epidemiology for Therapeutic Targets consortium (odds ratio, 1.13; 95% confidence interval, 0.89 to 1.42 per unit higher genetically predicted log FGF23) and the full BioVU sample (odds ratio, 1.32; 95% confidence interval, 0.95 to 1.84). In stratified analyses in BioVU, higher FGF23 was associated with overall heart failure (odds ratio, 3.09; 95% confidence interval, 1.38 to 6.91) among individuals with low eGFR-polygenic risk score (<1 SD below the mean), but not those with high eGFR-polygenic risk score ( We found no association between genetically predicted FGF23 and heart failure in the Heart Failure Molecular Epidemiology for Therapeutic Targets consortium. In BioVU, genetically elevated FGF23 was associated with higher heart failure risk, specifically heart failure with preserved ejection fraction, particularly among individuals with low genetically predicted eGFR. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_28_CJN00960122.mp3.
Sections du résumé
BACKGROUND AND OBJECTIVES
Elevated fibroblast growth factor-23 (FGF23) has been consistently associated with heart failure, particularly heart failure with preserved ejection fraction, among patients with CKD and in the general population. FGF23 may directly induce cardiac remodeling and heart failure. However, biases affecting observational studies impede robust causal inferences. Mendelian randomization leverages genetic determinants of a risk factor to examine causality. We performed a two-sample Mendelian randomization to assess causal associations between FGF23 and heart failure.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Genetic instruments were genome-wide significant genetic variants associated with FGF23, including variants near
RESULTS
Genetically determined FGF23 was not associated with overall heart failure in the Heart Failure Molecular Epidemiology for Therapeutic Targets consortium (odds ratio, 1.13; 95% confidence interval, 0.89 to 1.42 per unit higher genetically predicted log FGF23) and the full BioVU sample (odds ratio, 1.32; 95% confidence interval, 0.95 to 1.84). In stratified analyses in BioVU, higher FGF23 was associated with overall heart failure (odds ratio, 3.09; 95% confidence interval, 1.38 to 6.91) among individuals with low eGFR-polygenic risk score (<1 SD below the mean), but not those with high eGFR-polygenic risk score (
CONCLUSION
We found no association between genetically predicted FGF23 and heart failure in the Heart Failure Molecular Epidemiology for Therapeutic Targets consortium. In BioVU, genetically elevated FGF23 was associated with higher heart failure risk, specifically heart failure with preserved ejection fraction, particularly among individuals with low genetically predicted eGFR.
PODCAST
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_28_CJN00960122.mp3.
Identifiants
pubmed: 35902130
pii: 01277230-202208000-00013
doi: 10.2215/CJN.00960122
pmc: PMC9435988
doi:
Substances chimiques
Fibroblast Growth Factors
62031-54-3
Fibroblast Growth Factor-23
7Q7P4S7RRE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1183-1193Subventions
Organisme : NIGMS NIH HHS
ID : RC2 GM092618
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004798
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States
Organisme : NHLBI NIH HHS
ID : U19 HL065962
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025141
Pays : United States
Organisme : CSRD VA
ID : I01 CX001897
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122075
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM115305
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD074711
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS032830
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK035816
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006378
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Informations de copyright
Copyright © 2022 by the American Society of Nephrology.
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