Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
PLoS One. 2018 Dec 19;13(12):e0208654. doi: 10.1371/journal.pone.0208654. eCollection 2018.
To explore novel genetic loci for diabetic nephropathy, we performed genome-wide association studies (GWAS) for diabetic nephropathy in Japanese patients with type 2 diabetes. We analyzed the association of 5,768,242 single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes, 2,380 nephropathy cases and 5,234 controls. We further performed GWAS for diabetic nephropathy using independent Japanese patients with type 2 diabetes, 429 cases and 358 controls and the results of these two GWAS were combined with an inverse variance meta-analysis (stage-1), followed by a de novo genotyping for the candidate SNP loci (p < 1.0 × 10(-4)) in an independent case-control study (Stage-2; 1,213 cases and 1,298 controls). After integrating stage-1 and stage-2 data, we identified one SNP locus, significantly associated with diabetic nephropathy; rs56094641 in FTO, P = 7.74 × 10(-10). We further examined the association of rs56094641 with diabetic nephropathy in independent Japanese patients with type 2 diabetes (902 cases and 1,221 controls), and found that the association of this locus with diabetic nephropathy remained significant after integrating all association data (P = 7.62 × 10(-10)). We have identified FTO locus as a novel locus for conferring susceptibility to diabetic nephropathy in Japanese patients with type 2 diabetes.
为了探索糖尿病肾病的新遗传位点，我们对日本 2 型糖尿病患者的糖尿病肾病进行了全基因组关联研究（GWAS）。我们分析了 2380 例肾病病例和 5234 例对照中 5768242 个单核苷酸多态性（SNP）与日本 2 型糖尿病患者的关联。我们进一步对 429 例肾病病例和 358 例对照中独立的日本 2 型糖尿病患者进行了糖尿病肾病 GWAS，并对这两个 GWAS 的结果进行了逆方差荟萃分析（第一阶段），随后对候选 SNP 位点（p<1.0×10(-4))进行了从头基因分型的独立病例对照研究（第二阶段；1213 例病例和 1298 例对照）。在整合第一阶段和第二阶段的数据后，我们确定了一个与糖尿病肾病显著相关的 SNP 位点；FTO 中的 rs56094641，P=7.74×10(-10)。我们进一步在独立的日本 2 型糖尿病患者中检查了 rs56094641 与糖尿病肾病的关联（902 例病例和 1221 例对照），并发现该位点与糖尿病肾病的关联在整合所有关联数据后仍然显著（P=7.62×10(-10)）。我们已经确定 FTO 基因座是日本 2 型糖尿病患者易患糖尿病肾病的新基因座。
