A variant within the FTO confers susceptibility to diabetic nephropathy in Japanese patients with type 2 diabetes

• Published in: PloS one Vol. 13; no. 12; p. e0208654
• Main Authors: Taira, Makiko, Imamura, Minako, Takahashi, Atsushi, Kamatani, Yoichiro, Yamauchi, Toshimasa, Araki, Shin-Ichi, Tanaka, Nobue, van Zuydam, Natalie R, Ahlqvist, Emma, Toyoda, Masao, Umezono, Tomoya, Kawai, Koichi, Imanishi, Masahito, Watada, Hirotaka, Suzuki, Daisuke, Maegawa, Hiroshi, Babazono, Tetsuya, Kaku, Kohei, Kawamori, Ryuzo, Groop, Leif C, McCarthy, Mark I, Kadowaki, Takashi, Maeda, Shiro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19-12-2018; Public Library of Science (PLoS)
• Subjects: Aged; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; Basic Medicine; Bioinformatics; Biology and Life Sciences; Blood transfusions; Care and treatment; Case-Control Studies; Clinical Medicine; Complications and side effects; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - genetics; Diabetic nephropathies; Diabetic Nephropathies - genetics; Diabetic nephropathy; Diabetic retinopathy; Endocrinology; Endocrinology and Diabetes; Endokrinologi och diabetes; Female; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotyping; Health aspects; Hospitals; Humans; Internal medicine; Japan; Japanese (Asian people); Kidney diseases; Klinisk medicin; Laboratories; Loci; Male; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Metabolic disorders; Middle Aged; Nephrology; Nephropathy; Obesity; Patients; Physical Sciences; Polymorphism, Single Nucleotide; Research and Analysis Methods; Risk factors; Single-nucleotide polymorphism; Statistical analysis; Studies; Type 2 diabetes; University graduates; Variance analysis; Japan; Sweden; United Kingdom > UK; Okinawa; Finland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0208654

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.