జర్నల్ ఆఫ్ క్లినికల్ డయాబెటిస్

నైరూప్య

A Genome-wide Association Study in the Diabetic Patients Finds the 13q35.43-35.46 Locus Associated with Estimated Glomerular Filtration Rate: The Japan Multi-Institutional Collaborative Cohort Study

Yasuyuki Nakamura, Akira Narita, Tsuyoshi Hachiya, Yoichi Sutoh, Atsushi Shimizu, Seiko Ohno, Naoyuki Takashima, Harumitsu Suzuki, Keitaro Tanaka, Megumi Hara, Kiyonori Kuriki, Kaori Endoh, Isao Oze, Hidemi Ito, Hirokazu Uemura, Sakurako Katsuura-Kamano, Haruo Mikami, Yohko Nakamura, Ippei Shimoshikiryo, Toshiro Takezaki, Sadao Suzuki, Miki Watanabe, Na

Objective: To conduct a genome-wide association studies (GWAS) to find genetic variations that affected renal function in the diabetic patients in Japan.
Research design and methods: In a Japanese population of 955 patients with type 2 diabetes mellitus (T2D), extracted from 14,091 participants appropriate for GWAS from the Japan Multi-Institutional Collaborative Cohort (JMICC) study. Genotyping was performed at a central laboratory with use of a HumanOmniExpressExome-8 v1.2 BeadChip array. Genotype imputation was conducted with use of SHAPEIT, followed by Minimac3 software (with the 1000 Genomes phase 3 as the reference panel). We calculated the estimated glomerular filtration rate (eGFR) for each patient according to Matsuo et al. Association for the imputed variants with eGFR was performed by linear regression analysis with adjustments for age and sex.
Results: We found 77 SNVs upstream of the NBEA genes that were significantly associated with eGFR in T2D participants with P values <5 × 10^-8. This gene was reported as participatory in several metabolic functions and was associated with some disease conditions. However, no previous reports implied that the gene was related to nephropathy in diabetes.
Conclusion: We found the 13q35.43-35.46 locus upstream of the NBEA gene was significantly associated with eGFR in participants with T2D in a Japanese population.