03171nas a2200433 4500008004100000022001400041245007800055210006900133260001600202520191900218100003002137700002002167700001802187700001702205700001902222700001802241700002002259700002302279700002302302700002002325700002102345700002502366700002102391700001902412700001902431700002302450700001602473700002102489700002002510700002202530700002102552700002202573700001902595700002202614700002002636700002002656700002502676856003602701 2018 eng d a1533-345000aGenetic Variants Associated with Circulating Fibroblast Growth Factor 23.0 aGenetic Variants Associated with Circulating Fibroblast Growth F c2018 Sep 143 a
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 m 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 (=3.0×10), lies upstream of , 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 and upstream of (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 , 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.
1 aRobinson-Cohen, Cassianne1 aBartz, Traci, M1 aLai, Dongbing1 aIkizler, Alp1 aPeacock, Munro1 aImel, Erik, A1 aMichos, Erin, D1 aForoud, Tatiana, M1 aÅkesson, Kristina1 aTaylor, Kent, D1 aMalmgren, Linnea1 aMatsushita, Kunihiro1 aNethander, Maria1 aEriksson, Joel1 aOhlsson, Claes1 aMellström, Daniel1 aWolf, Myles1 aLjunggren, Osten1 aMcGuigan, Fiona1 aRotter, Jerome, I1 aKarlsson, Magnus1 aEcons, Michael, J1 aIx, Joachim, H1 aLutsey, Pamela, L1 aPsaty, Bruce, M1 ade Boer, Ian, H1 aKestenbaum, Bryan, R uhttps://chs-nhlbi.org/node/7774