Genotype-ocular Biometry Correlation Analysis of Eight Primary Angle Closure Glaucoma Susceptibility Loci in a Cohort from Northern China

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2018 Nov 7

PMID 30399154

Citations 7

Authors

Wenjuan Zhuang

Shaolin Wang

Juan Hao

Manyun Xu

Hao Chi

Shunyu Piao

Jianqing Ma

Xiaolong Zhang

Shaoping Ha

Affiliations

Soon will be listed here.

Abstract

Purpose: Recent genome-wide association studies (GWAS) have verified eight genetic loci that were significantly associated with primary angle-closure glaucoma (PACG). The present study investigated whether these variants are associated with the ocular biometric parameters of anterior chamber depth (ACD) and axial length (AL) in a northern Chinese population, as well as whether there were differences in the association of genetic markers in our cohort based on ethnicity.

Methods: A case-control association study of 500 patients and 720 controls was undertaken. All individuals were genotyped for eight single nucleotide polymorphisms (SNPs) (rs11024102 in PLEKHA7, rs3753841 in COL11A1, rs1015213 located between PCMTD1 and ST18, rs3816415 in EPDR1, rs1258267 in CHAT, rs736893 in GLIS3, rs7494379 in FERMT2, and rs3739821 mapping between DPM2 and FAM102A) using an improved multiplex ligation detection reaction (iMLDR) technique. Allelic and genotypic frequency differences were evaluated using a logistic regression model. Generalized estimation equation (GEE) analysis was conducted for association testing between genotypes and ocular biometric parameters. False discovery rate (FDR) correction for multiple comparisons was employed, and the statistical power was calculated via power and sample size calculation.

Results: Four of the eight SNPs, rs3753841, rs1258267, rs736893 and rs7494379, were associated with PACG (p = 0.007, 0.0016, 0.0045, 0.045, respectively), and only rs3753841, rs1258267 and rs736893 surpassed the FDR correction. For subgroup analysis, only rs1258267 could withstand multiple testing correction in the Han nationality (p = 0.00571). In the GEE tests, rs3753841, rs1258267 and rs736893 were found to be nominally associated with ACD (p = 0.023, 0.016, 0.01, respectively). However, these associations could not survive FDR correction.

Conclusions: The SNP rs3753841 in COL11A1, rs1258267 in CHAT and rs736893 in GLIS3 are associated with PACG in northern Chinese people, and the association of genetic markers manifests a tendency of ethnic diversity. Larger population-based studies are warranted to reveal additional PACG loci and ethnic aspects of PACG.

Citing Articles

Linking Iris Cis-Regulatory Variants to Primary Angle-Closure Glaucoma Via Clinical Imaging and Multiomics.

Li J, Chen Y, Wang W, Zhang Y, Su G, Wang S Invest Ophthalmol Vis Sci. 2024; 65(14):18.

PMID: 39652066 PMC: 11629910. DOI: 10.1167/iovs.65.14.18.

Publication trends of primary angle-closure disease during 1991-2022: a bibliometric analysis.

Huang H, Wang G, Wang K, Sun X Int J Ophthalmol. 2023; 16(5):800-810.

PMID: 37206181 PMC: 10172088. DOI: 10.18240/ijo.2023.05.19.

Pathways that affect anterior morphogenesis in embryos.

Boopathi B, Topalidou I, Kelley M, Meadows S, Funk O, Ailion M bioRxiv. 2023; .

PMID: 37163004 PMC: 10168279. DOI: 10.1101/2023.04.23.537986.

Genetic associations in and with primary angle-closure glaucoma susceptibility: A systematic review and meta-analysis.

Wang S, Zhang G, Lu H Indian J Ophthalmol. 2023; 71(2):343-349.

PMID: 36727317 PMC: 10228949. DOI: 10.4103/ijo.IJO_1226_22.

GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans.

Nair K, Srivastava C, Brown R, Koli S, Choquet H, Kang H Nat Commun. 2021; 12(1):4877.

PMID: 34385434 PMC: 8361148. DOI: 10.1038/s41467-021-25181-7.

References

Hanley J, Negassa A, Edwardes M, Forrester J . Statistical analysis of correlated data using generalized estimating equations: an orientation. Am J Epidemiol. 2003; 157(4):364-75. DOI: 10.1093/aje/kwf215. View

Vithana E, Khor C, Qiao C, Nongpiur M, George R, Chen L . Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma. Nat Genet. 2012; 44(10):1142-1146. PMC: 4333205. DOI: 10.1038/ng.2390. View

Lowe R . Primary angle-closure glaucoma. Inheritance and environment. Br J Ophthalmol. 1972; 56(1):13-20. PMC: 1208643. DOI: 10.1136/bjo.56.1.13. View

Quigley H, Broman A . The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006; 90(3):262-7. PMC: 1856963. DOI: 10.1136/bjo.2005.081224. View

Congdon N, Wang F, Tielsch J . Issues in the epidemiology and population-based screening of primary angle-closure glaucoma. Surv Ophthalmol. 1992; 36(6):411-23. DOI: 10.1016/s0039-6257(05)80022-0. View

He M, Wang D, Zheng Y, Zhang J, Yin Q, Huang W . Heritability of anterior chamber depth as an intermediate phenotype of angle-closure in Chinese: the Guangzhou Twin Eye Study. Invest Ophthalmol Vis Sci. 2008; 49(1):81-6. DOI: 10.1167/iovs.07-1052. View

Lowe R . Primary angle closure glaucoma: geographic and racial variations. Trans Ophthalmol Soc N Z. 1973; 25:81-4. View

Khor C, Do T, Jia H, Nakano M, George R, Abu-Amero K . Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. Nat Genet. 2016; 48(5):556-62. DOI: 10.1038/ng.3540. View

Lavanya R, Wong T, Friedman D, Aung H, Alfred T, Gao H . Determinants of angle closure in older Singaporeans. Arch Ophthalmol. 2008; 126(5):686-91. DOI: 10.1001/archopht.126.5.686. View

10.

Wright C, Tawfik M, Waisbourd M, Katz L . Primary angle-closure glaucoma: an update. Acta Ophthalmol. 2015; 94(3):217-25. DOI: 10.1111/aos.12784. View

11.

Lowe R . Aetiology of the anatomical basis for primary angle-closure glaucoma. Biometrical comparisons between normal eyes and eyes with primary angle-closure glaucoma. Br J Ophthalmol. 1970; 54(3):161-9. PMC: 1207665. DOI: 10.1136/bjo.54.3.161. View

12.

Kim Y, Nakanishi G, Lewandoski M, Jetten A . GLIS3, a novel member of the GLIS subfamily of Krüppel-like zinc finger proteins with repressor and activation functions. Nucleic Acids Res. 2003; 31(19):5513-25. PMC: 206473. DOI: 10.1093/nar/gkg776. View

13.

Foster P, Baasanhu J, Alsbirk P, Munkhbayar D, Uranchimeg D, Johnson G . Glaucoma in Mongolia. A population-based survey in Hövsgöl province, northern Mongolia. Arch Ophthalmol. 1996; 114(10):1235-41. DOI: 10.1001/archopht.1996.01100140435011. View

14.

Zeger S, Liang K, Albert P . Models for longitudinal data: a generalized estimating equation approach. Biometrics. 1988; 44(4):1049-60. View

15.

Amerasinghe N, Zhang J, Thalamuthu A, He M, Vithana E, Viswanathan A . The heritability and sibling risk of angle closure in Asians. Ophthalmology. 2010; 118(3):480-5. DOI: 10.1016/j.ophtha.2010.06.043. View

16.

Wang N, Wu H, Fan Z . Primary angle closure glaucoma in Chinese and Western populations. Chin Med J (Engl). 2003; 115(11):1706-15. View

17.

Alsbirk P . Primary angle-closure glaucoma. Oculometry, epidemiology, and genetics in a high risk population. Acta Ophthalmol Suppl. 1976; (127):5-31. View

18.

Nongpiur M, Cheng C, Duvesh R, Vijayan S, Baskaran M, Khor C . Evaluation of Primary Angle-Closure Glaucoma Susceptibility Loci in Patients with Early Stages of Angle-Closure Disease. Ophthalmology. 2018; 125(5):664-670. DOI: 10.1016/j.ophtha.2017.11.016. View

19.

Nongpiur M, Khor C, Jia H, Cornes B, Chen L, Qiao C . ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma. PLoS Genet. 2014; 10(3):e1004089. PMC: 3945113. DOI: 10.1371/journal.pgen.1004089. View

20.

Awadalla M, Thapa S, Hewitt A, Burdon K, Craig J . Association of genetic variants with primary angle closure glaucoma in two different populations. PLoS One. 2013; 8(6):e67903. PMC: 3695871. DOI: 10.1371/journal.pone.0067903. View