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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.

Original publication

DOI

10.1371/journal.pone.0208654

Type

Journal article

Journal

PloS one

Publication Date

01/2018

Volume

13

Addresses

Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

Keywords

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