Purchase this article with an account.
D. A. Schaumberg, W. G. Christen, M. M. DeAngelis, D. I. Chasman; Novel Associations of SNPs on Chromosomes 2 and 16 and Risk of Incident Neovascular Age-Related Macular Degeneration in the Women’s Genome Health Study. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1623.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Systematic analysis of prior genome-wide linkage studies has identified at least 5 regions of the genome that are significantly associated with age-related macular degeneration (AMD), including regions on chromosomes 1q, 2p, 3p, 10q, and 16q. Subsequent studies have shown clear evidence for association with the CFH gene on 1q, and with ARMS2/HTRA1 on 10q, but no associations have yet been discovered for the other significant linkage regions. We therefore sought to investigate these regions for AMD associated loci in a large prospective study.
We performed a positional candidate association analysis within the Women’s Genome Health Study assuming an additive genetic model for AMD focused on SNPs covering approximately 5% of the genome within 2p25.1-2p16.2, 3p25.3-3p14.1, and 16p13-16q23.1, regions identified as strong candidates by a prior meta-analysis of genome-wide linkage studies. Study participants included 23,294 women of confirmed European ancestry, among whom 161 developed AMD associated with a visual acuity reduction of 20/30 or worse over 12 y of follow-up, including 31 with neovascular AMD.
We identified two SNPs on chromosome 16 that were significantly associated with incident AMD when adjusted for the number of SNPs evaluated in this region: rs4887603 (incidence rate ratio [IRR]=3.39, 95% CI=1.97-5.82 for participants heterozygous for the risk allele; IRR=11.49, 95% CI=3.88-33.87 for homozygotes; corrected P-value=0.02), and rs1858993 (IRR=1.71, 95% CI=1.36-2.15 for heterozygotes; IRR=2.92, 95% CI=1.85-4.62 for homozygotes; corrected P-value=0.01). SNP rs1858993 on chromosome 16, with minor allele frequency=0.272, was also significantly associated with the neovascular form of AMD (IRR=3.25, 95% CI=1.98-5.38 for heterzygotes; IRR=10.56, 95% CI=3.92-28.94 for homozygotes; corrected P-value=0.007), and this association remained significant after adjusting for all SNPs in all evaluated regions combined. We also identified one regionally significant SNP on chromosome 2 associated with neovascular AMD: rs2693818 (IRR=3.39, 95% CI=1.84-6.26 for heterozygotes; IRR=11.49, 95% CI=3.39-39.19 for homozygotes; corrected P-value=0.04).
These data provide further evidence of an important AMD susceptibility locus on chromosome 16 and narrow the focus to the region of rs1858993, which is intergenic between LOC729993 and ERCC4 (a DNA repair gene). Confirmation in independent study populations is ongoing.
This PDF is available to Subscribers Only