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Meta-Analysis
. 2018 Oct;29(10):2583-2592.
doi: 10.1681/ASN.2018020192. Epub 2018 Sep 14.

Genetic Variants Associated with Circulating Fibroblast Growth Factor 23

Cassianne Robinson-Cohen  1 , Traci M Bartz  2 , Dongbing Lai  3 , T Alp Ikizler  4 , Munro Peacock  5 , Erik A Imel  5 , Erin D Michos  6 , Tatiana M Foroud  3 , Kristina Akesson  7   8 , Kent D Taylor  9 , Linnea Malmgren  7   8 , Kunihiro Matsushita  6   10   11 , Maria Nethander  12 , Joel Eriksson  13 , Claes Ohlsson  13 , Daniel Mellström  13 , Myles Wolf  14 , Osten Ljunggren  15 , Fiona McGuigan  7   8 , Jerome I Rotter  9 , Magnus Karlsson  7   8 , Michael J Econs  3   5 , Joachim H Ix  16   17 , Pamela L Lutsey  18 , Bruce M Psaty  19   20 , Ian H de Boer  21 , Bryan R Kestenbaum  21
Affiliations
Meta-Analysis

Genetic Variants Associated with Circulating Fibroblast Growth Factor 23

Cassianne Robinson-Cohen et al. J Am Soc Nephrol. 2018 Oct.

Abstract

Background: Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.

Methods: We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m2 to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR.

Results: We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0×10-24), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level.

Conclusions: Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.

Keywords: fibroblast growth factor 23; human genetics; mineral metabolism.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Manhattan plot of SNPs for FGF23. SNPs are plotted on the x axis according to their position on each chromosome against association with ln(FGF23) on the y axis (shown as –log10 P value).
See this image and copyright information in PMC

References

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