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

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Abstract

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.

Details

Authors
  • SUMMIT Consortium
  • 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
  • Leif C. Groop
  • Mark I. McCarthy
  • Takashi Kadowaki
  • Shiro Maeda
Organisations
External organisations
  • University of the Ryukyus
  • National Cerebral and Cardiovascular Center
  • Kyoto University
  • University of Tokyo
  • Tokyo Women's Medical University
  • University of Oxford
  • Juntendo University
  • Institute for Molecular Medicine Finland (FIMM)
  • University of Helsinki
  • RIKEN Center for Integrative Medical Sciences
  • University Hospital Of The Ryukyus
  • Shiga University of Medical Science
  • Tokai University
  • Kawai Clinic
  • Osaka City General Hospital
  • Ishikiri Seiki Hospital
  • Suzuki Diabetes Clinic
  • Kawasaki Medical School
  • Oxford University Hospital
  • Teikyo University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
  • Medical Genetics
Original languageEnglish
Article numbere0208654
JournalPLoS ONE
Volume13
Issue number12
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes