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

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


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cilia / genetics
  • Diabetic Retinopathy / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • RNA, Long Noncoding / genetics*


  • RNA, Long Noncoding

Grant support

This study was supported in part by a Grant-in-Aid for the Support Project of Strategic Research Center in Private Universities to the Saitama Medical University Research Center for Genomic Medicine from MEXT of Japan, research grants from National Center for Global Health and Medicine, and “Database Integration Coordination Program” from JST (Japan Science and Technology Agency). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.