講演情報
[P28-1]国際GWASメタ解析による小児ステロイド感受性ネフローゼ症候群の疾患感受性遺伝子の探索
○中山 真紀子1, Xiaoyuan Jia1,2, 河合 洋介1, 堀之内 智子3, 野津 寛大3, Seulgi Jung4, Kyuyong Song4, Hae Il Cheong5, 飯島 一誠3,6, 徳永 勝士1 (1.国立国際医療研究センター ゲノム医科学プロジェクト, 2.Renal Division, Peking University Shenzhen Hospital, Shenzhen, China, 3.神戸大学大学院 医学研究科 内科系講座 小児科学分野, 4.Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea, 5.Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea, 6.兵庫県立こども病院)
Background/objectives: Idiopathic nephrotic syndrome, which often responds to steroids, is the most common glomerular disease in children. To understand the genetic etiology, we conducted international genome-wide association studies (GWASs) in patients with steroid-sensitive nephrotic syndrome (SSNS). Methods: We recruited 1,018 children with SSNS and 3,331 Japanese ancestry controls, 249 children with SSNS and 4,041 controls with Korean ancestry. Japanese samples were genotyped by Affymetrix Japonica Array. Whole-genome imputation was performed using a phased reference panel of healthy Japanese individuals. Korean samples were processed by Axiom Genome-Wide ASI array and HumanOmni1-Quad BeadChip. Whole-genome imputation was performed using 1000 Genome project phase 3. Results: Japanese GWAS with 987 SSNS and 3,206 controls revealed significant loci, including HLA-DR/DQ (rs6901541, P = 2.80E-33, odds ratio [OR] = 2.49), NPHS1-KIRREL2 (rs56117924, P=4.94E-20, OR=1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72). Korean GWAS with 243 SSNS and 4,041 controls recapitulated the results in HLA-DR/DQ (rs9272518, P=1.04E-14, OR=2.63) and NPHS1-KIRREL2 (rs412175, P=4.65E-08, OR=1.83). Meta-analysis under fixed effects METAL demonstrated four loci to be significant; HLA-DR/DQ (rs114685974, P-meta=5.26E-39, OR=3.67), NPHS1-KIRREL2 (rs412175, P-meta=1.32E-24, OR=1.90), TNFSF15 (rs7848647, P-meta=5.20E-12, OR=1.43), and a new CD28-CTLA4 locus (rs1181388, P-meta=3.84E-10, OR=1.37). Conclusions: International GWASs elucidated novel loci associated with childhood SSNS.