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Editors Selection IGR 23-3
Optic Disc: Gene variants and OD parameters
Comment by Louis Pasquale on:
26808 A genome-wide association study of optic disc parameters, Ramdas WD; van Koolwijk LME; Ikram MK et al., PLoS Genetics, 2010; 6: 1-12
The main purpose of this work is toidentify common gene variants associated with optic disc area and verticalcup-disc ratio (vCDR). Secondary goalsincluded identifying genetic variants associated with open-angle glaucoma(OAG) and myopia. The study is appropriately powered to achieve its primary objectives. In the gene discovery phaseof the project, the investigators subjected DNA on 8,131 participants to high throughput genotyping in order to discover common gene variants associated with the quantitative traits of interest. Ramdas et al. (1079) used the Topcon ImageNet system to estimate the optic disc parameters in the discovery set. In assessing genetic variants associated with vCDR they appropriately adjusted their statistical model for glaucoma treatment, which may also affect this parameter.
High throughput genotyping reveals common genetic loci associated with optic disc area and vertical cup-disc ratio
Using this unbiased approach, the authors found three loci associated with optic disc area: CDC7/TGFBR3 region, ATOH7, and SALL1; and six with VCDR: CDKN2B, SIX1, SCYL1, CHEK2, ATOH7, and DCLK1. These results achieved statistical significance even after account for the 550,000 genetic tests that were performed simultaneously. Furthermore, these genetic loci were replicated in a second dataset consisting of 2,385 subjects. These results do have important ophthalmic implications. For example, in animal models where the ATOH7 gene (also known as Math5) is mutated,optic nerves and RGC fail to form properly.1 Furthermore, CDKN2B gene variants are associated with type-2 diabetes (T2D)2 and some studies suggest that T2D is associated with POAG.3,4 While there searchers were unable to definitively identify genes associated with OAG or myopia, they discovered a panel of genetic markers that point to potentially important biochemical pathways in various optic neuropathies.
References
- Brown NL, Patel S, Brzezinski J, Glaser T. Math5 is required for retinal ganglion cell and optic nerve formation. Development 2001;128:2497-508.
- Diabetes Genetics Initiative of Broad Institute Harvard and MIT et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 2007; 316:1331-6.
- Chopra V, Varma R, Francis BA et al. Type 2 diabetes mellitus and the risk of open-angle glaucoma: the Los Angeles Latino Eye Study. Ophthalmology 2008;115:227-232.
- Pasquale LR, Kang JH, Manson JE, et al. Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women. Ophthalmology 2006; 113:1081-6.
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