title: A genome-wide association study for diabetic retinopathy in a Japanese population: potential association with a long intergenic non-coding RNA.
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.
authors.affiliation: Department of Endocrinology and Diabetes, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Awata
authors.affiliation: Department of Endocrinology and Diabetes, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Hisakuni
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Endocrinology and Diabetes, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kurihara
authors.affiliation: Department of Endocrinology and Diabetes, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Morita-Ohkubo
authors.affiliation: Division of RI Laboratory, Biomedical Research Center, Saitama Medical University, Saitama, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyashita
authors.affiliation: Department of Endocrinology and Diabetes, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Katayama
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Saitama Medical University, Faculty of Medicine, Saitama, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Saitama Medical University, Faculty of Medicine, Saitama, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Yoneya
authors.affiliation: Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohda
authors.affiliation: Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.affiliation: Department of Internal Medicine, Saitama Social Insurance Hospital, Saitama, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Department of Internal Medicine, Saiseikai Central Hospital, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.affiliation: Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Research 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.
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Central Research Laboratory, Hitachi Ltd, Tokyo, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Koike
mesh_terms: D000328:Adult; D000368:Aged; D002923:Cilia / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding