Systems Biology approach for identification of glaucoma disease-associated genes and variants influence

Systems Biology approach


  • Jyoti Kant Choudhari CSTU
  • Tanushree Chatterjee


Glaucoma, open angle glaucoma, angle closure glaucoma, Gene-disease network


Glaucoma is a heterogeneous group of disease characterised by progressive optic nerve degeneration with a complex genetics basis.  It is broadly classified into primary and secondary based on their etiology and aqueous humor dynamics. Primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) occurs most commonly. In this study, disease-causing genes network was designed using cystoscope software. The DisGenNet plugin is used for mining the data from curated and BeFree database source. In this network, 89 (28.25 %) genes were reported with Genetic variation, Causal Mutation 6 (6.7%), Biomarker 220 (69.8%) in 25 subtypes of glaucoma. In this disease 179, genetic variations in 50 genes were associated with the glaucoma disease. Maximum gene found with intron variant around 38.70% followed by missense variant around 38.20%. In this study, it is found that a maximum number of the generic variation shown the modifier impact on the disease. The Designing gene-disease network helps in understanding the role of genes in the complex disease. It is a new approach to predict gene-disease association based on network analysis.  


1. Rao, K. N., Nagireddy, S., & Chakrabarti, S. (2011). Complex genetic mechanisms in glaucoma: an overview. Indian journal of ophthalmology, 59(7), 31.
2. Gemenetzi, M., Yang, Y., & Lotery, A. J. (2012). Current concepts on primary open-angle glaucoma genetics: a contribution to disease pathophysiology and future treatment. Eye, 26(3), 355-369.
3. Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P et al. Complement factor H variant increases the risk of age-related macular degeneration. Science 2005; 308: 419–421.
4. Choudhari, J. K., Choubey, J., Patel, A., & Verma, M. K. (2016). Molecular modeling and simulation analysis of glaucoma pathway. Network Modeling Analysis in Health Informatics and Bioinformatics, 5(1), 29.
5. Chang, D., Sha, Q., Zhang, X., Liu, P., Rong, S., Han, T., & Pan, H. (2011). The evaluation of the oxidative stress parameters in patients with primary angle-closure glaucoma. PLoS One, 6(11), e27218.
6. Kwon, Y. H., Fingert, J. H., Kuehn, M. H., & Alward, W. L. (2009). Primary open-angle glaucoma. New England Journal of Medicine, 360(11), 1113-1124.
7. Shields M., Ritch R. and Krupin T. 1996 Classification of the glaucomas. Mosby, St Louis, USA.
8. Quigley H. A. 1993 Open-angle glaucoma. N. Engl. J. Med. 328, 1097–1106.
9. Shields MB. 4th ed. New York: Lippincott Williams and Wilkins publishers; 2005. Shields’ Textbook of Glaucoma.
10. Sheffield, V. C., Stone, E. M., Alward, W. L., Drack, A. V., Johnson, A. T., Streb, L. M., & Nichols, B. E. (1993). Genetic linkage of familial open angle glaucoma to chromosome 1q21–q31. Nature genetics, 4(1), 47-50.
11. Sarfarazi, M., Child, A., Stoilova, D., Brice, G., Desai, T., Trifan, O. C., & Crick, R. P. (1998). Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region. The American Journal of Human Genetics, 62(3), 641-652.
12. Rezaie, T., Child, A., Hitchings, R., Brice, G., Miller, L., Coca-Prados, M., & Crick, R. P. (2002). Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science, 295(5557), 1077-1079.
13. Monemi, S., Spaeth, G., DaSilva, A., Popinchalk, S., Ilitchev, E., Liebmann, J.,& Sarfarazi, M. (2005). Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22. 1. Human molecular genetics, 14(6), 725-733.
14. Sharts-Hopko, N. C., & Glynn-Milley, C. (2009). PRIMARY OPEN‐ANGLE GLAUCOMA. AJN The American Journal of Nursing, 109 (2), 40-47.
15. Shannon, Paul, et al. "Cytoscape: a software environment for integrated models of biomolecular interaction networks." Genome research 13.11 (2003): 2498-2504.
16. Saito, Rintaro, et al. "A travel guide to Cytoscape plugins." Nature methods 9.11 (2012): 1069-1076.
17. Piñero, Janet, et al. "DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes." Database 2015 (2015): bav028.
18. 86. Hirschhorn JN, Daly MJ. Genome-wide association studies for common diseases and complex traits. Nat Rev Genet. 2005; 6:95–108. [PubMed: 15716906]
19. 87. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005; 308:385–9. [PMCID: PMC1512523] [PubMed: 15761122]
20. Bauer-Mehren, A., Rautschka, M., Sanz, F., & Furlong, L. I. (2010). DisGeNET: a Cytoscape plugin to visualize, integrate, search and analyze gene–disease networks. Bioinformatics, 26(22), 2924-2926.
21. Awadalla, M. S., Thapa, S. S., Hewitt, A. W., Burdon, K. P., & Craig, J. E. (2013). Association of genetic variants with primary angle closure glaucoma in two different populations. PloS one, 8(6), e67903.
22. Shastry, B. S. (2013). Genetic susceptibility to primary angle closure glaucoma (PACG). Discovery medicine, 15(80), 17-22.
23. Aponte, E. P., Diehl, N., & Mohney, B. G. (2010). Incidence and clinical characteristics of childhood glaucoma: a population-based study. Archives of ophthalmology, 128(4), 478-482.
24. Stoilov, I., Akarsu, A. N., & Sarfarazi, M. (1997). Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Human molecular genetics, 6(4), 641-647.
25. Reddy, A. B., Panicker, S. G., Mandal, A. K., Hasnain, S. E., & Balasubramanian, D. (2003). Identification of R368H as a predominant CYP1B1 allele causing primary congenital glaucoma in Indian patients. Investigative ophthalmology & visual science, 44(10), 4200-4203.
26. Chakrabarti, S., Kaur, K., Rao, K. N., Mandal, A. K., Kaur, I., Parikh, R. S., & Thomas, R. (2009). The transcription factor gene FOXC1 exhibits a limited role in primary congenital glaucoma. Investigative ophthalmology & visual science, 50(1), 75-83.
27. Ali, M., McKibbin, M., Booth, A., Parry, D. A., Jain, P., Riazuddin, S. A, & Gilmour, D. F. (2009). Null mutations in LTBP2 cause primary congenital glaucoma. The American Journal of Human Genetics
28. Pasutto, F., Matsumoto, T., Mardin, C. Y., Sticht, H., Brandstätter, J. H., Michels-Rautenstrauss, K., & Klaver, C. C. (2009). Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma. The American Journal of Human Genetics, 85(4), 447-456.




How to Cite

Choudhari, J. K., & Chatterjee, T. (2021). Systems Biology approach for identification of glaucoma disease-associated genes and variants influence: Systems Biology approach. CSVTU International Journal of Biotechnology, Bioinformatics and Biomedical, 6(01), 09–17. Retrieved from