人類血清FGF23濃度的全基因組相關研究

Abstract

研究背景 纖維母細胞生長因子家族成員目前發現有22種，這些蛋白質參與多種關鍵的生理功能，FGF23屬於FGF家族成員之一為內分泌賀爾蒙。近期發現纖維母細胞生長因子23（fibroblast growth factor 23, FGF23）有別於過去的認知，不只調節磷酸恆定和維生素D代謝，更參與多項代謝異常。遺傳研究有助於瞭解複雜性性狀與疾病的機轉，我們進行了台灣第一個全基因組關聯研究（GWAS），找尋影響血清FGF23濃度之基因位點。 研究方法 我們招募了來自Taiwan Biobank的5,000名參與者，進行了全基因組關聯研究（GWAS），利用酵素連結免疫吸附分析法測定血清FGF23的濃度。並使用PLINK v1.07中的additive genetic model進行GWAS分析。在排除患有糖尿病和品質控管未通過的參與者後，共分析了4201名受試者其單核苷酸多型性（SNP）與進行對數轉換的FGF23濃度的關聯，調整了年齡和性別。 結果 我們分析了4201位非糖尿病受試者，以P<1.0 x 10-6為閾值，找到3個SNP與血清FGF23濃度相關，位於PCSK9基因附近的SNP rs17111495、TGFβ2基因內的SNP rs2798631、HLA-DQA1基因附近的SNP rs17843626與血清中的FGF23水平顯示出統計學上的顯著關聯（分別為P = 4.88 x 10-10、P = 6.46 x 10-7和P = 3.74 x 10-8）。 結論 我們發現位於PCSK9基因附近、TGFβ2基因內、HLA-DQA1基因附近 SNP與華人血清中的FGF23濃度具有相關性。需要進一步的研究以支持我們的發現。

There are 22 members of the fibroblast growth factor family currently. These proteins are involved in many physiological functions. As endocrine hormone, FGF23 belongs to one of the members of the FGF family. Recent studies have found that fibroblast growth factor 23 (FGF23) is different from prior understanding. It not only regulates phosphate homeostasis and vitamin D metabolism but also participates in metabolic disturbances. Genetic studies are helpful to understand the complex traits and the mechanism of disease. We conducted the first whole genome association study (GWAS) in Taiwan to find genetic loci that affect serum FGF23 concentration. We recruited 5,000 participants from Taiwan Biobank. We performed a genome-wide association study (GWAS) and measured the concentration of serum FGF23 by enzyme-linked immunosorbent assay. GWAS analysis was performed by the additive genetic model in PLINK v1.07. After excluding participants with diabetes and failed quality control, a total of 4201 subjects were analyzed for associations between their single nucleotide polymorphisms (SNPs) and logarithmic FGF23 concentrations, adjusting for age and gender. We analyzed 4201 non-diabetic subjects. Using P <1.0 x 10-6 as the threshold, we found 3 SNPs that are related to serum FGF23 concentration. These associated SNPs are located at or adjacent to PCSK9, TGFβ2 and HLA-DQA1and show a statistically significant correlation with serum FGF23 levels (P = 4.88 x 10-10, P = 6.46 x 10-7, and P = 3.74 x 10-8, respectively).