title: Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population.
abstract: Primary open-angle glaucoma (POAG) is the major type of glaucoma. To discover genetic markers associated with POAG, we examined a total of 1,575 Japanese subjects in a genome-wide association study (stage 1) and a subsequent study (stage 2). Both studies were carried out at a single institution. In the stage 1 association study, we compared SNPs between 418 POAG patients and 300 control subjects. First, low-quality data were eliminated by a stringent filter, and 331,838 autosomal SNPs were selected for analysis. Poorly clustered SNPs were eliminated by a visual assessment, leaving 255 that showed a significant deviation (P < 0.001) in the allele frequency comparison. In the stage 2 analysis, we tested these 255 SNPs for association in DNA samples from a separate group of 409 POAG and 448 control subjects. High-quality genotype data were selected and used to calculate the combined P values of stages 1 and 2 by the Mantel-Haenszel test. These analyses yielded 6 SNPs with P < 0.0001. All 6 SNPs showed a significant association (P < 0.05) in stage 2, demonstrating a confirmed association with POAG. Although we could not link the SNPs to the annotated gene(s), it turned out that we have identified 3 genetic loci probably associated with POAG. These findings would provide the foundation for future studies to build on, such as for the metaanalysis, to reveal the molecular mechanism of the POAG pathogenesis.
authors.affiliation: Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nakano
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Takazumi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Tomohito
authors.initials: T
authors.lastname: Yagi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fuwa
authors.forename: Natsue
authors.initials: N
authors.lastname: Omi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tokuda
authors.forename: Masami
authors.initials: M
authors.lastname: Tanaka
authors.forename: Kengo
authors.initials: K
authors.lastname: Yoshii
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kageyama
authors.forename: Shigeta
authors.initials: S
authors.lastname: Naruse
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
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: D000328:Adult; D000368:Aged; D000594:Amino Acid Oxidoreductases / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human