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Baojian Fan, P. Ferdina Marie Sharmila, N. Soumittra, S. Sripriya, J. Madhavan, David S. Friedman, L. Vijaya, Jonathan L. Haines, Ronnie J. George, Janey L. Wiggs; Association of Polymorphisms near ATOH7 with Optic Disc Area in Indian Consanguineous Pedigrees. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3303. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Primary open angle glaucoma is a group of genetically complex disorders, which may have highly heritable quantitative traits as part of the overall phenotype. Mapping genes contributing to the related quantitative traits may effectively identify genetic risk factors predisposing to the complex disease. Allelic homozygosity in consanguineous pedigrees may enhance additive and/or subtractive effects of quantitative traits, creating greater variation for quantitative trait loci mapping. Recent genome-wide association studies identified several SNPs near the atonal homolog 7 (Drosophila) gene (ATOH7) associated with optic disc area and vertical cup-disc ratio (VCDR). The purpose of this study is to evaluate the association of these SNPs with optic nerve parameters in Indian consanguineous pedigrees.
Members of 2 Indian consanguineous pedigrees underwent a comprehensive ophthalmic examination for ocular quantitative traits such as intraocular pressure, central corneal thickness and curvature, optic disc size, optic cup size, visual acuity, and axial length. Four SNPs (rs4746741, rs1900004, rs3858145 and rs17231602) previously associated with optic disc area or VCDR were genotyped in 41 pedigree members. Family-based association was analyzed for the related quantitative traits.
Two SNPs, rs3858145 and rs17231602, were significantly associated with disc area (p=0.025 and 0.042 respectively). However, none of these four SNPs were associated with VCDR, cup area, mean retinal nerve fiber layer (RNFL) thickness, RNFL cross sectional area and 16 other related quantitative traits (p>0.05).
Our results confirm that genetic variants near ATOH7 are associated with optic disc area and that this result is generalizable to the South Indian population. In addition, our study shows that consanguineous pedigrees can provide sufficient power to detect genetic variants responsible for quantitative traits.
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