Genome-wide association study for circulating fibroblast growth factor 21 and 23

Gwo Tsann Chuang; Pi Hua Liu; Tsui Wei Chyan; Chen Hao Huang; Yu Yao Huang; Chia Hung Lin; Jou Wei Lin; Chih Neng Hsu; Ru Yi Tsai; Meng Lun Hsieh; Hsiao Lin Lee; Wei shun Yang; Cassianne Robinson-Cohen; Chia Ni Hsiung; Chen Yang Shen; Yi Cheng Chang

doi:10.1038/s41598-020-71569-8

Genome-wide association study for circulating fibroblast growth factor 21 and 23

Gwo Tsann Chuang, Pi Hua Liu, Tsui Wei Chyan, Chen Hao Huang, Yu Yao Huang, Chia Hung Lin, Jou Wei Lin, Chih Neng Hsu, Ru Yi Tsai, Meng Lun Hsieh, Hsiao Lin Lee, Wei shun Yang, Cassianne Robinson-Cohen, Chia Ni Hsiung, Chen Yang Shen, Yi Cheng Chang^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

8 Scopus citations

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.

Original language	English
Article number	14578
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-71569-8
State	Published - 01 12 2020

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Publisher Copyright:
© 2020, The Author(s).

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Chuang, G. T., Liu, P. H., Chyan, T. W., Huang, C. H., Huang, Y. Y., Lin, C. H., Lin, J. W., Hsu, C. N., Tsai, R. Y., Hsieh, M. L., Lee, H. L., Yang, W. S., Robinson-Cohen, C., Hsiung, C. N., Shen, C. Y., & Chang, Y. C. (2020). Genome-wide association study for circulating fibroblast growth factor 21 and 23. Scientific Reports, 10(1), Article 14578. https://doi.org/10.1038/s41598-020-71569-8

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title = "Genome-wide association study for circulating fibroblast growth factor 21 and 23",

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.",

author = "Chuang, {Gwo Tsann} and Liu, {Pi Hua} and Chyan, {Tsui Wei} and Huang, {Chen Hao} and Huang, {Yu Yao} and Lin, {Chia Hung} and Lin, {Jou Wei} and Hsu, {Chih Neng} and Tsai, {Ru Yi} and Hsieh, {Meng Lun} and Lee, {Hsiao Lin} and Yang, {Wei shun} and Cassianne Robinson-Cohen and Hsiung, {Chia Ni} and Shen, {Chen Yang} and Chang, {Yi Cheng}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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doi = "10.1038/s41598-020-71569-8",

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T1 - Genome-wide association study for circulating fibroblast growth factor 21 and 23

AU - Chuang, Gwo Tsann

AU - Liu, Pi Hua

AU - Chyan, Tsui Wei

AU - Huang, Chen Hao

AU - Huang, Yu Yao

AU - Lin, Chia Hung

AU - Lin, Jou Wei

AU - Hsu, Chih Neng

AU - Tsai, Ru Yi

AU - Hsieh, Meng Lun

AU - Lee, Hsiao Lin

AU - Yang, Wei shun

AU - Robinson-Cohen, Cassianne

AU - Hsiung, Chia Ni

AU - Shen, Chen Yang

AU - Chang, Yi Cheng

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

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Genome-wide association study for circulating fibroblast growth factor 21 and 23

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