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Ananth Viswanathan, Cristina Venturini, Pirro Hysi, Abhishek Nag, Ekaterina Yonova, Jie Wang, Tien Wong, Paul Healey, Paul Mitchell, Christopher Hammond; Clarifying the role of ATOH7 in glaucoma endophenotypes. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2651. doi: https://doi.org/.
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The ATOH7 gene has been previously associated with glaucoma and glaucoma-related traits such as cup/disc ratio and optic disc size. Cup/disc ratio is an important part of the glaucoma phenotype, whereas the relationship between the disease and optic disc size is weak and not well understood. The aim of this study was to investigate whether ATOH7 is associated primarily with cup/disc ratio or merely the size of the optic disc.
We carried out a genome wide association study (GWAS) on 1677 individuals over the age of 49 years from the Blue Mountains Eye Study with quantitative measurements for vertical disc diameter, vertical cup/disc ratio and intraocular pressure. The analyses were run for a candidate region around rs7916697 where ATOH7 gene lies. Three different linear regressions were performed with PLINK. The first was for vertical disc diameter adjusted on age, sex and intraocular pressure, the second for vertical cup/disc ratio adjusted on age, sex and intraocular pressure and the third for cup/disc ratio adjusted on age, sex, intraocular pressure and vertical disc diameter. We performed a replication analysis on a separate independent cohort of 1922 individuals (the TwinsUK cohort).
After adjustments for confounders, a strong signal of genome-wide significance was found at rs7916697 (beta=-3.779, pvalue=1.678x10-8) for vertical disc diameter. In addition rs7916697 was significant for vertical cup/disc ratio (beta= -0.019, pvalue= 2.43x10-4), adjusted on age, sex and intraocular pressure. However, the association signal at this SNP was not found in the analysis for vertical cup/disc ratio adjusted on age, sex, intraocular pressure and vertical disc diameter (beta=-0.007, pvalue= 0.148). Results were similar in the replication TwinsUK cohort.
The association signals at rs7916697 on ATOH7 are strong for vertical disc diameter and vertical cup/disc ratio, if the latter is not adjusted on vertical disc diameter. However, the signal for cup/disc ratio is lost when the analysis for cup/disc ratio is adjusted on disc diameter. This study finds that ATOH7 is associated with optic disc size but not cup/disc ratio.
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