Before release of individual data, p-value information was obtained directly from the AREDS dbGAP website. Of the 35 variants with P < 10-6 examined, 23 significantly modified risk of neovascular AMD. Many variants located in tandem on 1q32-q22 including those in CFH, CFHR4, CFHR2, CFHR5, F13B, ASPM and ZBTB were significantly associated with AMD risk. Of these variants, single SNP analysis revealed that CFH rs572515 was the most significantly associated with AMD risk (P < 10-6). Haplotype analysis supported our findings of single SNP association, demonstrating that the most significant haplotype, GATAGTTCTC, spanning CFH, CFHR4, and CFHR2 was associated with the greatest risk of developing neovascular AMD (P < 10-6). Other than variants on 1q32-q22, only two SNPs, rs9288410 (MAP2) on 2q34-q35 and rs2014307 (PLEKHA1/HTRA1) on 10q26 were significantly associated with AMD status (P = .03 and P < 10-6 respectively). After controlling for smoking history, gender and age, the most significant gene-gene interaction appears to be between rs10801575 (CFH) and rs2014307 (PLEKHA1/HTRA1) (P < 10-11). The best genotypic fit for rs10801575 and rs2014307 was an additive model based on LRT. After applying a Bonferonni correction, no other significant interactions were identified between any other SNPs.This is the first replication study on the NEI dbGAP SNPs, demonstrating that alleles on 1q, 2q and 10q may predispose an individual to AMD.Advanced age-related macular degeneration (AMD) is the most common cause of legal blindness in developed countries. Clinically two forms of advanced AMD are recognized: geographic atrophy and neovascular. Geographic atrophy is characterized by a slow progressive degeneration of the retinal pigment epithelium (RPE), resulting in the gradual loss of the photoreceptors. The neovascular form is characterized by the growth of new abnormal blood vessels from beneath the retina that can cause severe and rapid vision loss due to hemorrhage and exudation.