Genetic Variants Associated with Circulating Fibroblast Growth Factor 23
(2018) In Journal of the American Society of Nephrology: JASN 29(10). p.2583-2592- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2018-10
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of the American Society of Nephrology: JASN
- volume
- 29
- issue
- 10
- pages
- 10 pages
- publisher
- American Society of Nephrology
- external identifiers
-
- scopus:85054292082
- pmid:30217807
- ISSN
- 1533-3450
- DOI
- 10.1681/ASN.2018020192
- language
- English
- LU publication?
- yes
- id
- 0bfc1565-faab-4d8f-981d-859315beaf01
- date added to LUP
- 2018-10-10 17:30:10
- date last changed
- 2025-02-04 19:33:27
@article{0bfc1565-faab-4d8f-981d-859315beaf01, abstract = {{<p>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.</p><p>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.</p><p>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.</p><p>CONCLUSIONS: Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.</p>}}, author = {{Robinson-Cohen, Cassianne and Bartz, Traci M and Lai, Dongbing and Ikizler, T Alp and Peacock, Munro and Imel, Erik A and Michos, Erin D and Foroud, Tatiana M and Akesson, Kristina and Taylor, Kent D and Malmgren, Linnea and Matsushita, Kunihiro and Nethander, Maria and Eriksson, Joel and Ohlsson, Claes and Mellström, Daniel and Wolf, Myles and Ljunggren, Osten and McGuigan, Fiona and Rotter, Jerome I and Karlsson, Magnus and Econs, Michael J and Ix, Joachim H and Lutsey, Pamela L and Psaty, Bruce M and de Boer, Ian H and Kestenbaum, Bryan R}}, issn = {{1533-3450}}, language = {{eng}}, number = {{10}}, pages = {{2583--2592}}, publisher = {{American Society of Nephrology}}, series = {{Journal of the American Society of Nephrology: JASN}}, title = {{Genetic Variants Associated with Circulating Fibroblast Growth Factor 23}}, url = {{http://dx.doi.org/10.1681/ASN.2018020192}}, doi = {{10.1681/ASN.2018020192}}, volume = {{29}}, year = {{2018}}, }