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PLoS By Category | Recent PLoS Articles
Neurological Disorders - Ophthalmology

Common Variants on Chromosome 9p21 Are Associated with Normal Tension Glaucoma
Published: Thursday, July 05, 2012
Author: Mitsuko Takamoto et al.

by Mitsuko Takamoto, Toshikatsu Kaburaki, Akihiko Mabuchi, Makoto Araie, Shiro Amano, Makoto Aihara, Atsuo Tomidokoro, Aiko Iwase, Fumihiko Mabuchi, Kenji Kashiwagi, Shiroaki Shirato, Noriko Yasuda, Hidetoshi Kawashima, Fumiko Nakajima, Jiro Numaga, Yoshiya Kawamura, Tsukasa Sasaki, Katsushi Tokunaga

Although intraocular pressure (IOP) is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG) termed normal tension glaucoma (NTG), which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS). We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value?=?7.40×?10-8, odds ratio (OR) ?=?2.00 with 95% confidence interval (CI) 1.55–2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p?=?4.96?×?10-11, OR ?=?2.13 with 95% CI 1.69–2.68). The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG), the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.
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