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Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese
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. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japane...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299784/ https://www.ncbi.nlm.nih.gov/pubmed/22428042 http://dx.doi.org/10.1371/journal.pone.0033389 |
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author | Nakano, Masakazu Ikeda, Yoko Tokuda, Yuichi Fuwa, Masahiro Omi, Natsue Ueno, Morio Imai, Kojiro Adachi, Hiroko Kageyama, Masaaki Mori, Kazuhiko Kinoshita, Shigeru Tashiro, Kei |
author_facet | Nakano, Masakazu Ikeda, Yoko Tokuda, Yuichi Fuwa, Masahiro Omi, Natsue Ueno, Morio Imai, Kojiro Adachi, Hiroko Kageyama, Masaaki Mori, Kazuhiko Kinoshita, Shigeru Tashiro, Kei |
author_sort | Nakano, Masakazu |
collection | PubMed |
description | 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. METHODS AND PRINCIPAL FINDINGS: 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 AND SIGNIFICANCE: 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. |
format | Online Article Text |
id | pubmed-3299784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32997842012-03-16 Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese Nakano, Masakazu Ikeda, Yoko Tokuda, Yuichi Fuwa, Masahiro Omi, Natsue Ueno, Morio Imai, Kojiro Adachi, Hiroko Kageyama, Masaaki Mori, Kazuhiko Kinoshita, Shigeru Tashiro, Kei PLoS One Research Article 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. METHODS AND PRINCIPAL FINDINGS: 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 AND SIGNIFICANCE: 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. Public Library of Science 2012-03-12 /pmc/articles/PMC3299784/ /pubmed/22428042 http://dx.doi.org/10.1371/journal.pone.0033389 Text en Nakano et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nakano, Masakazu Ikeda, Yoko Tokuda, Yuichi Fuwa, Masahiro Omi, Natsue Ueno, Morio Imai, Kojiro Adachi, Hiroko Kageyama, Masaaki Mori, Kazuhiko Kinoshita, Shigeru Tashiro, Kei Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese |
title | Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese |
title_full | Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese |
title_fullStr | Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese |
title_full_unstemmed | Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese |
title_short | Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese |
title_sort | common variants in cdkn2b-as1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in japanese |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299784/ https://www.ncbi.nlm.nih.gov/pubmed/22428042 http://dx.doi.org/10.1371/journal.pone.0033389 |
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