|Title:||Genome-wide association study for circulating fibroblast growth factor 21 and 23||Authors:||GWO-TSANN CHUANG
|Issue Date:||2020||Publisher:||NATURE RESEARCH||Journal Volume:||10||Journal Issue:||1||Source:||Scientific reports||Abstract:||
Fibroblast growth factors (FGFs) 21 and 23 are recently identified hormones regulating metabolism of glucose, lipid, phosphate and vitamin D. Here we conducted a genome-wide association study (GWAS) for circulating FGF21 and FGF23 concentrations to identify their genetic determinants. We enrolled 5,000 participants from Taiwan Biobank for this GWAS. After excluding participants with diabetes mellitus and quality control, association of single nucleotide polymorphisms (SNPs) with log-transformed FGF21 and FGF23 serum concentrations adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for body mass index (BMI) and a third model additionally adjusted for BMI and estimated glomerular filtration rate (eGFR) were used. A total of 4,201 participants underwent GWAS analysis. rs67327215, located within RGS6 (a gene involved in fatty acid synthesis), and two other SNPs (rs12565114 and rs9520257, located between PHC2-ZSCAN20 and ARGLU1-FAM155A respectively) showed suggestive associations with serum FGF21 level (P = 6.66 × 10-7, 6.00 × 10-7 and 6.11 × 10-7 respectively). The SNPs rs17111495 and rs17843626 were significantly associated with FGF23 level, with the former near PCSK9 gene and the latter near HLA-DQA1 gene (P = 1.04 × 10-10 and 1.80 × 10-8 respectively). SNP rs2798631, located within the TGFB2 gene, was suggestively associated with serum FGF23 level (P = 4.97 × 10-7). Additional adjustment for BMI yielded similar results. For FGF23, further adjustment for eGFR had similar results. We conducted the first GWAS of circulating FGF21 levels to date. Novel candidate genetic loci associated with circulating FGF21 or FGF23 levels were found. Further replication and functional studies are needed to support our findings.
biological marker; FGF21 protein, human; fibroblast growth factor; fibroblast growth factor 23; vitamin D; adult; aged; blood; body mass; female; genetics; genome-wide association study; human; male; middle aged; single nucleotide polymorphism; Taiwan; Adult; Aged; Biomarkers; Body Mass Index; Female; Fibroblast Growth Factors; Genome-Wide Association Study; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Taiwan; Vitamin D
|Appears in Collections:||醫學系|
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