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Article: Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study
Title | Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study |
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Authors | |
Keywords | FGF23 Cardiovascular disease Cardiovascular risk factor Type 2 diabetes mellitus Longevity Kidney disease Mendelian randomization |
Issue Date | 2021 |
Publisher | Frontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/genetics |
Citation | Frontiers in Genetics, 2021, v. 12, article no. 699455 How to Cite? |
Abstract | Introduction: Fibroblast growth factor 23 (FGF23), a potential biomarker for kidney function, is related to cardiovascular disease (CVD) and diabetes, although it is unclear whether the relation is causal. This study evaluated the associations of genetically predicted FGF23 with major CVDs, their risk factors, kidney function, and longevity using Mendelian randomization (MR).
Methods: This is a two-sample MR study using summary statistics from large genome-wide association studies. Primary outcomes included coronary artery disease (CAD), myocardial infarction, heart failure, and atrial fibrillation. Secondary outcomes included cardiovascular risk factors, kidney function, and longevity. We used four single-nucleotide polymorphisms (SNPs) predicting FGF23, excluding rs2769071 in the ABO gene, which likely violates the MR exclusion-restriction assumption. We used inverse-variance weighted (IVW) as the primary statistical method to assess associations of FGF23 with the outcomes. Sensitivity analyses included weighted median (WM) and MR-Egger. We repeated the analyses including all five SNPs. Last, we validated the positive findings from the main analyses in a smaller study, i.e., FinnGen.
Results: Using IVW, genetically predicted higher FGF23 was inversely associated with risk of CAD [odds ratio (OR): 0.69 per logtransformed FGF23 (pg/ml) increase, 95% confidence interval (CI): 0.52–0.91] and type 2 diabetes mellitus (T2DM) (OR: 0.70, 95% CI: 0.52–0.96), but not with the other outcomes. The WM and MR-Egger estimates were directionally consistent.
Conclusion: This study suggests that genetically predicted higher FGF23 may be protective against CAD and T2DM. Future studies should explore the underlying mechanisms related to the potential protective effect of FGF23. FGF23 was unlikely a cause of poorer renal function. |
Persistent Identifier | http://hdl.handle.net/10722/304596 |
ISSN | 2023 Impact Factor: 2.8 2023 SCImago Journal Rankings: 0.853 |
PubMed Central ID | |
ISI Accession Number ID | |
Errata |
DC Field | Value | Language |
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dc.contributor.author | Liang, Y | - |
dc.contributor.author | Luo, S | - |
dc.contributor.author | Schooling, CM | - |
dc.contributor.author | Au Yeung, SL | - |
dc.date.accessioned | 2021-10-05T02:32:24Z | - |
dc.date.available | 2021-10-05T02:32:24Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Frontiers in Genetics, 2021, v. 12, article no. 699455 | - |
dc.identifier.issn | 1664-8021 | - |
dc.identifier.uri | http://hdl.handle.net/10722/304596 | - |
dc.description.abstract | Introduction: Fibroblast growth factor 23 (FGF23), a potential biomarker for kidney function, is related to cardiovascular disease (CVD) and diabetes, although it is unclear whether the relation is causal. This study evaluated the associations of genetically predicted FGF23 with major CVDs, their risk factors, kidney function, and longevity using Mendelian randomization (MR). Methods: This is a two-sample MR study using summary statistics from large genome-wide association studies. Primary outcomes included coronary artery disease (CAD), myocardial infarction, heart failure, and atrial fibrillation. Secondary outcomes included cardiovascular risk factors, kidney function, and longevity. We used four single-nucleotide polymorphisms (SNPs) predicting FGF23, excluding rs2769071 in the ABO gene, which likely violates the MR exclusion-restriction assumption. We used inverse-variance weighted (IVW) as the primary statistical method to assess associations of FGF23 with the outcomes. Sensitivity analyses included weighted median (WM) and MR-Egger. We repeated the analyses including all five SNPs. Last, we validated the positive findings from the main analyses in a smaller study, i.e., FinnGen. Results: Using IVW, genetically predicted higher FGF23 was inversely associated with risk of CAD [odds ratio (OR): 0.69 per logtransformed FGF23 (pg/ml) increase, 95% confidence interval (CI): 0.52–0.91] and type 2 diabetes mellitus (T2DM) (OR: 0.70, 95% CI: 0.52–0.96), but not with the other outcomes. The WM and MR-Egger estimates were directionally consistent. Conclusion: This study suggests that genetically predicted higher FGF23 may be protective against CAD and T2DM. Future studies should explore the underlying mechanisms related to the potential protective effect of FGF23. FGF23 was unlikely a cause of poorer renal function. | - |
dc.language | eng | - |
dc.publisher | Frontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/genetics | - |
dc.relation.ispartof | Frontiers in Genetics | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | FGF23 | - |
dc.subject | Cardiovascular disease | - |
dc.subject | Cardiovascular risk factor | - |
dc.subject | Type 2 diabetes mellitus | - |
dc.subject | Longevity | - |
dc.subject | Kidney disease | - |
dc.subject | Mendelian randomization | - |
dc.title | Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study | - |
dc.type | Article | - |
dc.identifier.email | Luo, S: aprilluo@hku.hk | - |
dc.identifier.email | Schooling, CM: cms1@hkucc.hku.hk | - |
dc.identifier.email | Au Yeung, SL: ayslryan@hku.hk | - |
dc.identifier.authority | Schooling, CM=rp00504 | - |
dc.identifier.authority | Au Yeung, SL=rp02224 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3389/fgene.2021.699455 | - |
dc.identifier.pmid | 34367258 | - |
dc.identifier.pmcid | PMC8343174 | - |
dc.identifier.scopus | eid_2-s2.0-85112658287 | - |
dc.identifier.hkuros | 325873 | - |
dc.identifier.volume | 12 | - |
dc.identifier.spage | article no. 699455 | - |
dc.identifier.epage | article no. 699455 | - |
dc.identifier.isi | WOS:000681630600001 | - |
dc.publisher.place | Switzerland | - |
dc.relation.erratum | doi:10.3389/fgene.2021.794246 | - |
dc.relation.erratum | eid:eid_2-s2.0-85120403501 | - |