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S.K. Iyengar, G. Jun, K.E. Lee, R. Klein, B.E. K. Klein; A Complex Genetic Model for a Locus on 1p36 for Cortical Cataracts in the Beaver Dam Eye Study . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2516.
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© ARVO (1962-2015); The Authors (2016-present)
While cortical cataract is the second most common type of age–related cataract, its molecular genetics and pathogenesis is largely unknown.
We conducted a genome–wide scan (GWS) with 2252 individuals (N=1009 sibpairs) from 487 pedigrees in the Beaver Dam Eye Study (BDES). We performed a model–free linkage analysis using a quantitative trait for cortical cataract adjusted for covariates, both untransformed and transformed.
For the most significant regions in the GWS, we tested linkage heterogeneity by removing chromosome linked sib pairs. We assessed gene–gene and gene–environment interactions for the markers with the nominal P 0.01. We obtained evidence for linkage on 1p36 (D1S3669; p=8.3x10–4), 1p21 (D1S1631; p=6.7x10–5), 1q31 (D1S1660; p=1.3x10–4), 3q13 (D3S2460; p=1.8x10–4), 5q22 (D5S2501; p=2.4x10–5), 12q24 (D12S1045; p=7.1x10–5), and 21q22 (D21S1446; p=1.2x10–6) in the GWS, either with untransformed or transformed phenotype. Removal of 117 linked pairs on 1p36 revealed heterogeneity on 1q31 (D1S1677; before removal (BR): 0.15, after removal (AR): 9x10–4) and on 1q41 (D1S2141; BR: 0.0088, AR: 5x10–7). Linkage signals best explained by smoking were on 1p36 (main effect (ME): 0.17, interaction (I): 1x10–4) and 1p21 (ME: 0.33, I: 0.008). Significant gene–gene interactions with the marker D1S3669 were observed on 2q11 (ME: 0.003, I: 6x10–4), 3q13 (ME: 0.99, I: 7x10–7), 6q16 (ME: 0.19, I: 6x10–5), 8q13 (ME: 0.065, I: 4x10–4), 14q22 (ME: 0.023, I: 3x10–6), 14q14 (ME: 0.003, I: 5x10–5), and 21q22 (ME: 0.65; I: 3x10–4). We recognize that multiple testing is an issue and permutation tests are being conducted.
The 1p36 region for cortical cataract is involved in linkage heterogeneity, as well as in gene–gene and gene–environment interaction.
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