Single Marker Associations of Cell Cycle Pathway Genes With Advanced AMD

Abstract

Purpose:: To examine the association of allelic variants in cell cycle pathway genes with advanced age-related macular degeneration (AMD).

Methods:: We applied data from a whole-genome case-control association study to analyze single nucleotide polymorphisms (SNPs) from 50 healthy elderly people without AMD, 50 people with neovascular AMD (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 gene catalogue and the Ensembl and NCBI databases to identify all SNPs on a microarray with positional markers in cell cycle pathway 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 180 SNPs in regions of 60 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.

Results:: One marker for CGA and advanced AMD (NV AMD + CGA) emerged in our additive models. Cell Cycle-AMD relationships were not observed for NV AMD.

Conclusions:: These novel findings demonstrate an association between a variant in a cell cycle pathway gene and advanced AMD. Results will be validated in gene set analyses with forthcoming data from the Age-Related Eye Disease Study (AREDS).

Keywords: age-related macular degeneration • gene microarray • genetics