PLoS One. 2014 Nov 3;9(11):e111715. doi: 10.1371/journal.pone.0111715.

A genome-wide association study for diabetic retinopathy in a Japanese population: potential association with a long intergenic non-coding RNA.

Awata T1, Yamashita H1, Kurihara S1, Morita-Ohkubo T1, Miyashita Y2, Katayama S1, Mori K3, Yoneya S3, Kohda M4, Okazaki Y4, Maruyama T5, Shimada A6, Yasuda K7, Nishida N8, Tokunaga K9, Koike A10.
  • 1Department of Endocrinology and Diabetes, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
  • 2Division of RI Laboratory, Biomedical Research Center, Saitama Medical University, Saitama, Japan.
  • 3Department of Ophthalmology, Faculty of Medicine, Saitama Medical University, Faculty of Medicine, Saitama, Japan.
  • 4Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
  • 5Department of Internal Medicine, Saitama Social Insurance Hospital, Saitama, Japan.
  • 6Department of Internal Medicine, Saiseikai Central Hospital, Tokyo, Japan.
  • 7Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
  • 8Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 9Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 10Central Research Laboratory, Hitachi Ltd, Tokyo, Japan.

Corresponding author:

Takuya Awata, Professor, Department of Diabetes, Endocrinology and Metabolism, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara-shi, Tochigi, 329-2763, Japan

Tel: +81-287-39-3060, Fax: +81-287-39-3001 E-mail: awatatakuya@iuhw.ac.jp

 

Abstract

Elucidation of the genetic susceptibility factors for diabetic retinopathy (DR) is important to gain insight into the pathogenesis of DR, and may help to define genetic risk factors for this condition. In the present study, we conducted a three-stage genome-wide association study (GWAS) to identify DR susceptibility loci in Japanese patients, which comprised a total of 837 type 2 diabetes patients with DR (cases) and 1,149 without DR (controls). From the stage 1 genome-wide scan of 446 subjects (205 cases and 241 controls) on 614,216 SNPs, 249 SNPs were selected for the stage 2 replication in 623 subjects (335 cases and 288 controls). Eight SNPs were further followed up in a stage 3 study of 297 cases and 620 controls. The top signal from the present association analysis was rs9362054 in an intron of RP1-90L14.1 showing borderline genome-wide significance (Pmet = 1.4×10(-7), meta-analysis of stage 1 and stage 2, allele model). RP1-90L14.1 is a long intergenic non-coding RNA (lincRNA) adjacent to KIAA1009/QN1/CEP162 gene; CEP162 plays a critical role in ciliary transition zone formation before ciliogenesis. The present study raises the possibility that the dysregulation of ciliary-associated genes plays a role in susceptibility to DR.

PMID: 25364816

 

 

 

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