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Ocular Genetics


Ocular-Genetics1Research is focused on understanding the genetic basis and biochemical mechanisms of hereditary eye diseases, and includes the study of inherited glaucoma subtypes, corneal dystrophies, retinal dystrophies and myopia. Particular attention is given to eye diseases and phenotypes common to Asia such as primary angle closure glaucoma and myopia.

Both parametric and non parametric locus/gene mapping methods are carried out to identify novel disease genes disease susceptible loci as well as quantitative traits of ocular diseases. Candidate genes and novel genes are screened to identify novel mutations and to carry out genotype-phenotype correlations for ocular diseases more prevalent within the main racial groups of Asia. One of the main goals is to establish ethnic/race specific disease database that contain both clinical and genetic information for identification of genetic markers with diagnostic, prognostic or pharmacological value.

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Glaucoma
At SERI we study primary open angle glaucoma (POAG), primary angle-closure glaucoma (PACG), pseudo exfoliation glaucoma (PXG) and congenital glaucoma. In order to elucidate the full allelic spectrum for both POAG and PACG, we plan to conduct large scale GWAS, exome arrays, whole genome sequencing and interrogate related quantitative traits. For the development of a diagnostic and prognostic risk stratification model for POAG and PACG we plan to incorporate genomic as well as demographic, environmental and endophenotypic (clinical and imaging parameters) information. We also aim to investigate whether the recently identified PACG genetic variants are also associated with early stages of angle closure disease or are involved in susceptibility to disease progression. In addition, we plan to characterize the function of the newly identified PACG susceptibility genes to provide insights into disease pathogenesis that will enable future development of novel effective therapies. In order to adequately power genomic discoveries and conduct large scale meta- analyses we have entered into several regional and international collaborations to share data from GWASs on glaucoma and related quantitative traits. The International Glaucoma Genetics Consortium (IGGC) has been established for POAG, while for PACG we are leading a global PACG genetic consortium with investigators from across the globe. Additionally we have conducted GWAS studies on PXG and have identified further genetic variants for the condition.

Corneal Diseases
To study genetic basis of numerous corneal dystrophies including congenital hereditary endothelial dystrophy (CHED), more frequently occurring Fuch’s corneal dystrophy (FCD), keratoconus and Bowman’s membrane and stromal corneal dystrophies (SCD).

Since 2004 the Ocular Genomics Group has produced more than 90 peer-reviewed papers in leading journals in Genetics and Ophthalmology such as Nature Genetics, Plos Genetics, Human Molecular Genetics and Ophthalmology.

  1. Vithana EN*, Chen Y*, Lin Y*, Jia L*, … Khor CC, Pang CP#, Sun X#, Yang Z#. Common genetic variants near the ABCA1 gene and in the PMM2 gene are associated with primary open-angle glaucoma. Nat Genetics (*Joint first authors). Nat Genet. 2014; Oct;46(10):1115-9
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  3. Hysi PG*, Cheng CY*, Springelkamp H*, Macgregor S*, Bailey JNC*, Wojciechowski R*, Vitart V, Nag A, Hewitt AW, Höhn R, Venturini C, Mirshahi A, Ramdas WD, Thorleifsson G, Vithana E, Khor CC, Stefansson AB, et al ……………… Wong T-Y, BMES GWAS Group, NEIGHBORHOOD Consortium, Wellcome Trust Case Control Consortium, Viswanathan A*, Mackey DA*, Craig JE*, Wiggs JL*, van Duijn CM*, Hammond CJ*‡, Aung T*‡. Genome-wide Analysis of Multiethnic Cohorts Identifies Four New Loci Influencing Susceptibility to Increased Intraocular Pressure and Susceptibility to Glaucoma. Nat. Genet 2014
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  5. Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R , Chen L-J, Do T, Huang CK, Abu-Amero K, Low S, Tajudin LSA, Perera SA, // Simmons CP, Bei J-X, Zeng Y-X, Foster PJ, Vijaya L, Wong TY, Pang CP, Wang N, Aung T. Genome-wide association analyses identify three new susceptibility loci for Primary Angle Closure Glaucoma. Nat Genet 2012 Oct; 44(10):1142-6
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  7. Vithana EN, Morgan P, Sundaresan P, Ebenezer ND, Tan DT, Mohamed MD, Anand S, Khine KO, Venkataraman D, Yong VH, Salto-Tellez M, Venkatraman A, Guo K, Hemadevi B, Srinivasan M, Prajna V, Khine M, Casey JR, Inglehearn CF, Aung T. Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2). Nat Genet. 2006 Jul;38(7):755-7
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  9. Li Z, Allingham RR, et al….. …Wiggs JL, Khor CC, Yang Z, Pang CP, Wang N, Hauser MA, Tashiro K, Aung T, Vithana EN. A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet. 2015 Jul 1;24(13):3880-92
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  11. Cornes BK, Khor CC, Nongpiur ME, Xu L, Tay W-T, Zheng Y, Lavanya R, Li Y, Wu R, Sim X, Wang Y-X, Chen P, Teo YY, Chia K-S, Seielstad M, Liu JJ, Hibberd ML, Cheng C-Y, Saw SM, Tai E-S, Jonas JB, Vithana EN, Wong TY, Aung T. Identification of Four Novel Variants That Influence Central Corneal Thickness in Multi-Ethnic Asian Populations. Hum Mol Genet. 2012; 21(2):437-45
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  13. Khor CC*, Ramdas WD*, Vithana EN*, Cornes BK, Sim X, Tay W-T, Saw S-M, Zheng Y, Lavanya R, Wu R, Wang JJ, Mitchell P, Uitterlinden AG, Rivadeneira F, Teo YY, Chia KS, Seielstad M, Hibberd M, Vingerling JR, Klaver CCW, Jansonius NM, Tai E-S, Wong TY, van Duijn CM, Aung T. Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area. Hum Mol Genet. 2011; 20(9):1864-72
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  15. Nongpiur ME*, Khor CC* , Jia H*, …, Pang CP#, Vithana EN#, Wang N#, and Aung T #. ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma. Plos Genet. (# Joint last authors) 2014; Mar 6; 10(3):e1004089
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  17. Trikha S, Saffari E, Nongpiur M, Baskaran M, Ho H, Li Z, Tan P-Y, Khor CC, Perera SA, Cheng CY, Aung T*, Vithana E*. Genetic variant in TGFBR3-CDC7 is associated with visual field progression in primary open angle glaucoma patients from Singapore. Ophthalmology. 2015 Dec;122(12):2416-22
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  19. Lee MC*, Chan AS*, Goh SR, Hilmy MH, Nongpiur ME, Hong W, Aung T, Hunziker W, Vithana EN. Expression of the primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 in endothelial and epithelial cell junctions in the eye. Invest Ophthalmol Vis Sci. 2014; May 6;55(6):3833-41


Head: A/Prof Eranga Vithana

Co-Investigators/Collaborators: Prof Aung Tin, Prof Wong Tien Yin, A/Prof Cheng Ching-Yu, Dr Baskaran Mani, Dr JJ Liu (GIS/NUS), Dr CC Khor (GIS/NUS), Dr Monisha Esther Nongpiur, A/Prof Jodbhir Mehta

Research Staff (Post Doctoral Scientist): Dr Lee Mei Chin

Research Staff (Research Officers): Victor Yong, Ng Xiao Yu, Yaan Fun, Yue Ming Chen, Goh Shuang Ru, William Shei

Contact Us: A/Prof Eranga Vithana at eranga.nishanthie.vithana@seri.com.sg