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J. P. SanGiovanni, E. Y. Chew, T. E. Clemons, A. K. Henning, J. Hoh, M. Elashoff; Single Marker Associations of Nuclear-Encoded Mitochondrial Genes With Advanced AMD . Invest. Ophthalmol. Vis. Sci. 2007;48(13):2086. doi: https://doi.org/.
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To examine the association of allelic variants in nuclear-encoded mitochondrial (mt) genes with advanced AMD.
We applied data from a whole-genome case-control association study to interrogate SNPs of nuclear-encoded mt genes from 50 healthy elderly people without AMD, 50 people with neovascular (NV) AMD, and 46 people with central geographic atrophy (CGA). Details of the study design, outcome ascertainment, genomic profiling, and participant characteristics exist in Klein et al. (Science; 308:385. 2005). We used a curated mt gene catalogue and the Ensembl and NCBI databases to identify 1593 SNPs on our microarray with positional markers in nuclear-encoded mt gene regions. Final analyses were restricted to SNPs that met our data quality filters (based on call frequency and Hardy-Weinberg equilibrium); this amounted to 1329 SNPs in regions of 433 nuclear-encoded mt genes. We compared allele combinations of these SNPs in healthy controls to those in people with advanced AMD. A p-value threshold of 0.002 for allelic association with AMD was determined from a false discovery rate analysis.
Two markers for advanced AMD (NV AMD + CGA) emerged when we modeled the association of allele frequency with disease. One marker existed each for NV AMD and CGA. In all cases SNPs were located in non-coding regions.
These novel findings demonstrate an association of variants in nuclear-encoded mt genes with advanced AMD. Results will be validated with forthcoming data from AREDS.
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