Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study

IntroductionFibroblast 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...

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Autores principales:	Ying Liang, Shan Luo, C. Mary Schooling, Shiu Lun Au Yeung
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	FGF23 cardiovascular disease cardiovascular risk factor type 2 diabetes mellitus longevity kidney disease Genetics QH426-470
Acceso en línea:	https://doaj.org/article/c2fdbabfacae42e594b1f479c839729d
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spelling	oai:doaj.org-article:c2fdbabfacae42e594b1f479c839729d2021-11-08T17:35:11ZGenetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study1664-802110.3389/fgene.2021.699455https://doaj.org/article/c2fdbabfacae42e594b1f479c839729d2021-07-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.699455/fullhttps://doaj.org/toc/1664-8021IntroductionFibroblast 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).MethodsThis 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.ResultsUsing 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.ConclusionThis 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.Ying LiangShan LuoC. Mary SchoolingC. Mary SchoolingShiu Lun Au YeungFrontiers Media S.A.articleFGF23cardiovascular diseasecardiovascular risk factortype 2 diabetes mellituslongevitykidney diseaseGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FGF23 cardiovascular disease cardiovascular risk factor type 2 diabetes mellitus longevity kidney disease Genetics QH426-470
spellingShingle	FGF23 cardiovascular disease cardiovascular risk factor type 2 diabetes mellitus longevity kidney disease Genetics QH426-470 Ying Liang Shan Luo C. Mary Schooling C. Mary Schooling Shiu Lun Au Yeung Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study
description	IntroductionFibroblast 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).MethodsThis 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.ResultsUsing 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.ConclusionThis 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.
format	article
author	Ying Liang Shan Luo C. Mary Schooling C. Mary Schooling Shiu Lun Au Yeung
author_facet	Ying Liang Shan Luo C. Mary Schooling C. Mary Schooling Shiu Lun Au Yeung
author_sort	Ying Liang
title	Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study
title_short	Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study
title_full	Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study
title_fullStr	Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study
title_full_unstemmed	Genetically Predicted Fibroblast Growth Factor 23 and Major Cardiovascular Diseases, Their Risk Factors, Kidney Function, and Longevity: A Two-Sample Mendelian Randomization Study
title_sort	genetically predicted fibroblast growth factor 23 and major cardiovascular diseases, their risk factors, kidney function, and longevity: a two-sample mendelian randomization study
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c2fdbabfacae42e594b1f479c839729d
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_version_	1718441514564059136

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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