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

PLoS One. 2018 Dec 19;13(12):e0208654. doi: 10.1371/journal.pone.0208654. eCollection 2018.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Nephropathies / genetics*
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human

Grant support

This work was partly supported by a grant from the Ministry of Education, Culture, Science and Technology, Japan (to SM), and from the Japan Agency of Medical Research and Development (17km0405202h0802) (TK, TY, SM). The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) for the Innovative Medicine Initiative under grant agreement n° 115006, the SUMMIT Consortium.