Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population.
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.
Nakano
Masakazu
M
Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Ikeda
Yoko
Y
Taniguchi
Takazumi
T
Yagi
Tomohito
T
Fuwa
Masahiro
M
Omi
Natsue
N
Tokuda
Yuichi
Y
Tanaka
Masami
M
Yoshii
Kengo
K
Kageyama
Masaaki
M
Naruse
Shigeta
S
Matsuda
Akira
A
Mori
Kazuhiko
K
Kinoshita
Shigeru
S
Tashiro
Kei
K
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
D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human