PLoS ONE (Jan 2018)

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

  • Makiko Taira,
  • Minako Imamura,
  • Atsushi Takahashi,
  • Yoichiro Kamatani,
  • Toshimasa Yamauchi,
  • Shin-Ichi Araki,
  • Nobue Tanaka,
  • Natalie R van Zuydam,
  • Emma Ahlqvist,
  • Masao Toyoda,
  • Tomoya Umezono,
  • Koichi Kawai,
  • Masahito Imanishi,
  • Hirotaka Watada,
  • Daisuke Suzuki,
  • Hiroshi Maegawa,
  • Tetsuya Babazono,
  • Kohei Kaku,
  • Ryuzo Kawamori,
  • SUMMIT Consortium,
  • Leif C Groop,
  • Mark I McCarthy,
  • Takashi Kadowaki,
  • Shiro Maeda

DOI
https://doi.org/10.1371/journal.pone.0208654
Journal volume & issue
Vol. 13, no. 12
p. e0208654

Abstract

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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.