Singapore Scientists Perform The First Asian-Based Genome-Wide Association Study On Optic Disc Area

Singapore Scientists Perform The First Asian-Based Genome-Wide Association Study On Optic Disc Area
Main Category: Eye Health / Blindness
Also Included In: Genetics
Article Date: 25 Feb 2011 - 1:00 PST




A team of scientists from Singapore is the first to identify a new gene that controls optic disc1 area, and confirm that two genes2 previously reported to govern optic disc size in Europeans are also key players in Singapore Malays and Indians. This study, the first genome-wide association study (GWAS) on optic disc area ever to be conducted on Asians, was jointly conducted by scientists from the Genome Institute of Singapore (GIS), an institute of Singapore's Agency of Science, Technology and Research (A*STAR), the Singapore Eye Research Institute (SERI), the National University of Singapore (NUS), as well as colleagues from Rotterdam in the Netherlands, the USA and Australia. As previous studies have suggested that optic disc area may be an indicator of susceptibility to glaucoma, a deeper understanding of what influences optic disc area may help in predicting a patient's susceptibility to the disease. The work was published in the journal Human Molecular Genetics.

Glaucoma, an eye disorder in which the nerve carrying information from the eye to the brain suffers damage, accounts for 40 percent of blindness in Singapore. It primarily affects the elderly and middle aged - the disorder affects three percent of the population aged over 50, and 10 percent of the population aged over 70. A better understanding of how optic disc area affects one's susceptibility to glaucoma may help clinicians better manage the disease.

"The aim of this study is to identify genes for optic disc area that may be unique in Asian populations as well as genes shared with Caucasians", said GIS Research Fellow and one of the first authors of the paper, Dr Khor Chiea Chuen. "It is remarkable that despite major differences in the genetic make-up and the anatomy of the eyes between the Asian and Caucasian populations, we were able to discover three major genes that play a role in individuals from these different ethnicities."

He added, "The effort in conducting genetic studies in our own Singaporean cohorts have to continue, as we are now showing that Singaporeans have a unique genetic make-up, and better understanding of this would make the goal of 'personalised medicine' not so remote in the near future."

"Optic nerve area is regarded as an intermediate phenotype or 'endophenotype' for primary angle glaucoma (POAG). There is now a growing trend to interrogate the genes that control the glaucoma endophenotypes, to see if they are associated with the disease/POAG itself. Our efforts are adding more and more genes to this growing list of potential POAG genes, which can then be evaluated to see whether they (the genes) make a significant contribution to the risk of POAG", said Prof Eranga N. Vithana, Head of Ocular Genomics, Assistant Director, Basic and Experimental Sciences at the SERI.

Associate Professor Aung Tin, Deputy Director, SERI and Head Glaucoma Service, SNEC, added, "The Singapore Eye Research Institute, in collaboration with the Genome Institute of Singapore, has genotyped more than 7,000 Singaporeans in order to determine the genes underlying eye traits and dimensions. This study has just identified a new gene for the optic nerve, which is the site of damage of eye diseases such as glaucoma, the leading cause of irreversible blindness worldwide. This discovery was subsequently replicated in samples from Holland."

"The findings are interesting as the gene may be involved in glaucoma; this is the subject of further research. We hope that this is the first of many discoveries of novel genes in the future that has been made possible by large population studies conducted in Singapore by SERI," he added.

Prof Adrian Hill, Professor of Human Genetics at Oxford University commented, "This is a very large and impressive study on optic disc size that adds considerably to our knowledge of the genetics of this area".

Their research involved more than 4,000 individuals drawn from two ethnic populations in Singapore, with replication in Rotterdam, the Netherlands, involving the data of close to 10,000 European individuals. The two ethnic populations were drawn from the Singapore Malay Eye Study (SiMES), and the Singapore Indian Eye Study (SINDI).

1 The optic disc or nerve head is the location where ganglion cell axons exit the eye to form the optic nerve.

2 The scientists found a new gene on chromosome CARD10, which strongly associates with optic disc area in both Singapore cohorts as well as in the Rotterdam Study. They also confirmed the association between the genes ATOH7 and TGFBR3 and optic disc area in Asians.

Notes

Research publication:

The research findings described in the press release can be found in the 2011 advance online issue of Human Molecular Genetics under the title "Genome-wide association studies in Asians confirm the involvement of AT0H7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area".

Authors:

Chiea Chuen Khor1,2,3* Wishal D. Ramdas4,5*, Eranga N. Vithana2,6* , Belinda K Cornes2, Xueling Sim3, Wan-Ting Tay2, Seang-Mei Saw2,3,6,7, Yingfeng Zheng2, Raghavan Lavanya2, Renyi Wu2, Jie Jin Wang8,9, Paul Mitchell8, André G. Uitterlinden4,10 Fernando Rivadeneira4, Yik-Ying Teo3,7, Kee-Seng Chia3,7, Mark Seielstad11, Martin Hibberd,1,7 Johannes R. Vingerling 4,5, Caroline C.W. Klaver4,5, Nomdo M. Jansonius4,12, E-Shyong Tai3,7,13, Tien-Yin Wong2,6,7,8, Cornelia M. van Duijn4, Tin Aung2,6†

1. Infectious Diseases, Genome Institute of Singapore, A*STAR, Singapore;

2. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore;

3. NUS-GIS Center for Molecular Epidemiology, Singapore;

4. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

5. Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands

6. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

7.Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;

8. Centre for Eye Research Australia, University of Melbourne, Victoria, Australia.

9. Centre for Vision Research, University of Sydney, NSW, Australia.

10. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands

11.Institute for Human Genetics & Department of Laboratory Medicine, University of California, San Francisco, United States of America

12. Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

13. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;

* These authors contributed equally and are joint first authors

Source:
Genome Institute of Singapore
Singapore Eye Research Institute
Agency for Science, Technology and Research (A*STAR)

Singapore Scientists Perform The First Asian-Based Genome-Wide Association Study On Optic Disc Area