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Genetic Analysis Of Japanese Primary Open-angle Glaucoma Patients And Clinical Characterization Of Risk Alleles Near CDKN2B-AS1, SIX6 And GAS7

Yukihiro Shiga, K. Nishiguchi, Yosuke Kawai, K. Kojima, K. Sato, K. Fujita, Mai Takahashi, Kazuko Omodaka, M. Araie, K. Kashiwagi, M. Aihara, T. Iwata, F. Mabuchi, M. Takamoto, M. Ozaki, K. Kawase, N. Fuse, M. Yamamoto, J. Yasuda, M. Nagasaki, T. Nakazawa
Published 2017 · Medicine

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Purpose To test the genetic association between Japanese patients with primary open-angle glaucoma (POAG) and the previously reported POAG susceptibility loci and to perform genotype–phenotype analysis. Methods Genetic associations for 27 SNPs from 16 loci previously linked to POAG were assessed using genome-wide SNP data of the primary cohort (565 Japanese POAG patients and 1,104 controls). Reproducibility of the assessment was tested in 607 POAG cases and 455 controls (second cohort) with a targeted genotyping approach. For POAG-associated variants, a genotype–phenotype correlation study (additive, dominant, recessive model) was performed using the objective clinical data derived from 598 eyes of 598 POAG patients. Results Among 27 SNPs from 16 loci previously linked to POAG, genotypes for total of 20 SNPs in 13 loci were available for targeted association study. Among 8 SNPs in 3 loci that showed at least nominal association (P < 5.00E-02) in the primary cohort, a representative SNP for each loci (rs2157719 for CDKN2B-AS1, rs33912345 for SIX6, and rs9913911 for GAS7) were selected. For these SNPs the association was found significant in both the second cohort analysis and meta-analysis. The genotype–phenotype analysis revealed significant correlations between CDKN2B-AS1 (rs2157719) and decreased intraocular pressure (β = -6.89 mmHg, P = 1.70E-04; dominant model) after multiple corrections. In addition, nominal correlation was observed between CDKN2B-AS1 (rs2157719) and optic nerve head blood flow (β = -0.54 and -0.67 arbitrary units (AU), P = 2.00E-02 and 1.39E-02), between SIX6 (rs33912345) and decreased total peripapillary retinal nerve fiber layer thickness (β = -2.16 and -2.82 μm, P = 4.68E-02 and 2.40E-02, additive and recessive model, respectively) and increased optic nerve head blood flow (β = 0.44 AU, P = 2.20E-02; additive model) and between GAS7 (rs9913911) and increased cup volume (β = 0.03 mm3, P = 4.60E-02) and mean cup depth (β = 0.03 mm3, P = 4.11E-02; additive model) and decreased pattern standard deviation (β = -0.87 dB, P = 2.44E-02; dominant model). Conclusion The association between SNPs near GAS7 and POAG was found in Japanese patients for the first time. Clinical characterization of the risk variants is an important step toward understanding the pathology of the disease and optimizing treatment of patients with POAG.
This paper references
10.1093/hmg/dds103
A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma.
W. Osman (2012)
10.1038/ng.824
Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1
K. Burdon (2011)
10.1111/ceo.12354
Usefulness of novel laser speckle flowgraphy‐derived variables of the large vessel area in the optic nerve head in normal tension glaucoma
Shigeto Maekawa (2014)
10.1016/j.ajo.2012.07.023
CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States.
L. Pasquale (2013)
10.1038/ncomms9018
Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals
M. Nagasaki (2015)
10.1016/S0014-4835(05)80094-6
Non-contact, two-dimensional measurement of tissue circulation in choroid and optic nerve head using laser speckle phenomenon.
Y. Tamaki (1995)
10.1038/ng.3087
Genome-wide analysis of multiethnic cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma
P. Hysi (2014)
A genome-wide association study in the Japanese population confirms 9 p 21 and 14 q 23 as susceptibility loci for primary open angle glaucoma
W. Osman (2012)
Genome - wide association analysis identifies TXNRD 2 , ATXN 2 and FOXC 1 as susceptibility loci for primary open - angle glaucoma
JN Bailey (2016)
10.1371/journal.pone.0099138
Stereoscopic Analysis of Optic Nerve Head Parameters in Primary Open Angle Glaucoma: The Glaucoma Stereo Analysis Study
Y. Yokoyama (2014)
10.1016/j.ophtha.2011.03.012
Myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis.
M. Marcus (2011)
Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO 1 and CDKN 2 BAS 1
K. Burdon (2011)
10.1016/j.ophtha.2012.02.004
Glaucoma risk alleles at CDKN2B-AS1 are associated with lower intraocular pressure, normal-tension glaucoma, and advanced glaucoma.
K. Burdon (2012)
[Analysis of choroidal blood flow by laser speckle flowgraphy].
H. Isono (1997)
10.1001/archopht.1994.01090130079022
Family history and risk of primary open angle glaucoma. The Baltimore Eye Survey.
J. Tielsch (1994)
10.1186/1471-2415-14-113
Correlation between structure/function and optic disc microcirculation in myopic glaucoma, measured with laser speckle flowgraphy
N. Aizawa (2014)
10.2147/OPTH.S22097
Association between optic nerve blood flow and objective examinations in glaucoma patients with generalized enlargement disc type
N. Chiba (2011)
10.1371/journal.pgen.1002654
Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma
J. Wiggs (2012)
10.1167/iovs.13-12930
Waveform analysis of ocular blood flow and the early detection of normal tension glaucoma.
Yukihiro Shiga (2013)
10.1034/J.1600-0420.2003.00073.X
Relationship between optic nerve head microcirculation and visual field loss in glaucoma.
K. Yaoeda (2003)
10.1167/iovs.14-15373
Laser speckle and hydrogen gas clearance measurements of optic nerve circulation in albino and pigmented rabbits with or without optic disc atrophy.
N. Aizawa (2014)
CDKN 2 BAS 1 genotype - glaucoma feature correlations in primary open - angle glaucoma patients from the United States
LR Pasquale (2013)
10.2188/jea.JE20150268
The Tohoku Medical Megabank Project: Design and Mission
Shinichi 進一 Kuriyama 栗山 (2016)
10.1038/ng.661
Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma
G. Thorleifsson (2010)
The apolipoprotein E gene polymorphism is associated with open angle glaucoma in the Japanese population.
F. Mabuchi (2005)
10.1111/j.1755-3768.1975.tb01135.x
APPLANATION TONOMETRY AND CENTRAL CORNEAL THICKNESS
N. Ehlers (1975)
10.3109/02713683.2015.1127974
Optic Nerve Head Blood Flow, as Measured by Laser Speckle Flowgraphy, Is Significantly Reduced in Preperimetric Glaucoma
Yukihiro Shiga (2016)
10.1016/j.ophtha.2009.12.001
Genome-wide association study of normal tension glaucoma: common variants in SRBD1 and ELOVL5 contribute to disease susceptibility.
A. Meguro (2010)
Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma
Guðmar Þorleifsson (2010)
10.1371/journal.pone.0033389
Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese
M. Nakano (2012)
10.1073/pnas.0906397106
Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population
M. Nakano (2009)
10.1371/journal.pgen.1004372
Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma
Megan Ulmer Carnes (2014)
10.1155/2014/468908
Correlation of Optic Nerve Microcirculation with Papillomacular Bundle Structure in Treatment Naive Normal Tension Glaucoma
W. Kobayashi (2014)
10.1167/iovs.14-15863
Association of common SIX6 polymorphisms with peripapillary retinal nerve fiber layer thickness: the Singapore Chinese Eye Study.
C. Cheng (2014)
10.1093/hmg/ddv128
A common variant near TGFBR3 is associated with primary open angle glaucoma
Z. Li (2015)
10.1038/jhg.2015.68
Japonica array: improved genotype imputation by designing a population-specific SNP array with 1070 Japanese individuals
Yosuke Kawai (2015)
10.1167/iovs.13-12013
Longitudinal hemodynamic changes within the optic nerve head in experimental glaucoma.
G. Cull (2013)
10.1167/iovs.12-10911
Anterior and posterior optic nerve head blood flow in nonhuman primate experimental glaucoma model measured by laser speckle imaging technique and microsphere method.
L. Wang (2012)
10.1038/ng.3078
Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma
Y. Chen (2014)
10.1136/bjo.2005.081224
The number of people with glaucoma worldwide in 2010 and 2020
H. Quigley (2006)
10.1016/J.OPHTHA.2006.03.059
Risk factors for open-angle glaucoma in a Japanese population: the Tajimi Study.
Y. Suzuki (2006)
10.1038/ng.3482
Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open angle glaucoma
J. C. Bailey (2016)
10.1371/journal.pone.0040107
Common Variants on Chromosome 9p21 Are Associated with Normal Tension Glaucoma
M. Takamoto (2012)
10.1007/s00439-013-1349-5
Genome-wide association study and meta-analysis of intraocular pressure
A. B. Ozel (2013)
10.1016/S1350-9462(02)00008-3
The impact of ocular blood flow in glaucoma
J. Flammer (2002)
10.1371/journal.pgen.1002611
Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma
L. V. van Koolwijk (2012)
10.1016/j.ajo.2015.04.001
Quantitative Trait Locus Analysis of SIX1-SIX6 With Retinal Nerve Fiber Layer Thickness in Individuals of European Descent.
J. Kuo (2015)
10.1097/APO.0000000000000183
Ocular Blood Flow and Influencing Factors for Glaucoma
T. Nakazawa (2016)
10.1167/IOVS.03-0516
Heritability of risk factors for primary open-angle glaucoma: the Beaver Dam Eye Study.
B. Klein (2004)
10.1038/ng.3079
Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma
P. Gharahkhani (2014)
10.3109/02713683.2013.807932
Simulated Visual Fields Produced from Macular RNFLT Data in Patients with Glaucoma
Mai Takahashi (2013)



This paper is referenced by
10.1167/iovs.19-27396
Cyclin-Dependent Kinase Inhibitor 2b Attenuates Excitotoxicity-Induced Death of Retinal Ganglion Cells.
Hiroshi Tawarayama (2019)
10.1038/s41598-019-57066-7
Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study
Yong Woo Kim (2020)
10.1016/j.exer.2018.11.005
All roads lead to glaucoma: Induced retinal injury cascades contribute to a common neurodegenerative outcome.
Samih Alqawlaq (2019)
10.1186/s13104-019-4491-x
Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case–control study
Altaf A. Kondkar (2019)
10.1093/jb/mvy096
Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare
J. Yasuda (2019)
10.1038/s41467-019-09304-9
Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density
Erna V. Ivarsdottir (2019)
10.1167/iovs.18-26489
Association of Polymorphisms at the SIX1-SIX6 Locus With Primary Open-Angle Glaucoma.
Shi Yao Lu (2019)
10.18388/abp.2018_2639
Circular and long non-coding RNAs and their role in ophthalmologic diseases.
Olga Wawrzyniak (2018)
10.1167/iovs.61.10.37
Association of Glaucoma Risk Genes with Retinal Nerve Fiber Layer in a Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study
Xiaoran Chai (2020)
10.26508/lsa.201900528
In vivo and in vitro knockout system labelled using fluorescent protein via microhomology-mediated end joining
Shota Katayama (2019)
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