title: Common variants in CDKN2B-AS1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese.
abstract: BACKGROUND
  To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated.
  
  
  RESULTS
  We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8 × 10(-10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)--POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)--and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients.
  
  
  CONCLUSIONS
  In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.
authors.affiliation: Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nakano
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tokuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fuwa
authors.forename: Natsue
authors.initials: N
authors.lastname: Omi
authors.forename: Morio
authors.initials: M
authors.lastname: Ueno
authors.forename: Kojiro
authors.initials: K
authors.lastname: Imai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Adachi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kageyama
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Mori
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Kei
authors.initials: K
authors.lastname: Tashiro
mesh_terms: D044466:Asian People; D016022:Case-Control Studies; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D005901:Glaucoma / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics* / Q000502:physiology; D007564:Japan / Q000453:epidemiology; D009900:Optic Nerve / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated