Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, 5F, No.2, Xuzhou Rd., Zhongzheng Dist., Taipei, 100, Taiwan, ROC.
Sci Rep. 2020 Sep 3;10(1):14578. doi: 10.1038/s41598-020-71569-8.
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, 6.00 × 10 and 6.11 × 10 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 and 1.80 × 10 respectively). SNP rs2798631, located within the TGFB2 gene, was suggestively associated with serum FGF23 level (P = 4.97 × 10). 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.
成纤维细胞生长因子 (FGFs) 21 和 23 是最近发现的调节葡萄糖、脂质、磷酸盐和维生素 D 代谢的激素。在这里，我们进行了一项针对循环 FGF21 和 FGF23 浓度的全基因组关联研究 (GWAS)，以确定其遗传决定因素。我们从台湾生物库招募了 5000 名参与者进行这项 GWAS。在排除患有糖尿病和质量控制的参与者后，我们分析了单核苷酸多态性 (SNP) 与经年龄、性别和祖先主成分调整后的 FGF21 和 FGF23 血清浓度之间的关联。第二个模型还额外调整了体重指数 (BMI)，第三个模型还额外调整了 BMI 和估计肾小球滤过率 (eGFR)。共有 4201 名参与者进行了 GWAS 分析。rs67327215 位于 RGS6 内（参与脂肪酸合成的基因），另外两个 SNP(rs12565114 和 rs9520257，分别位于 PHC2-ZSCAN20 和 ARGLU1-FAM155A 之间) 与血清 FGF21 水平呈显著相关性（P=6.66×10，6.00×10 和 6.11×10）。SNP rs17111495 和 rs17843626 与 FGF23 水平显著相关，前者靠近 PCSK9 基因，后者靠近 HLA-DQA1 基因（P=1.04×10 和 1.80×10）。SNP rs2798631 位于 TGFB2 基因内，与血清 FGF23 水平呈显著相关性（P=4.97×10）。进一步调整 BMI 得到了类似的结果。对于 FGF23，进一步调整 eGFR 也得到了类似的结果。我们进行了迄今为止针对循环 FGF21 水平的首次 GWAS。发现了与循环 FGF21 或 FGF23 水平相关的新候选遗传基因座。需要进一步的复制和功能研究来支持我们的发现。
