A search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways

Several lines of inquiry point to overlapping molecular mechanisms between late-onset Alzheimer disease (AD) and age-related macular degeneration (AMD). We evaluated summarized results from large genome-wide association studies for AD and AMD to test the hypothesis that AD susceptibility loci are also associated with AMD. We observed association of both disorders with genes in a region of chromosome 7, including PILRA and ZCWPW1 (peak AMD SNP rs7792525, minor allele frequency [MAF]= 19%, odds ratio [OR]= 1.14, p= 2.34× 10^-6), and with ABCA7 (peak AMD SNP rs3752228, MAF= 0.054, OR= 1.22, p= 0.00012). Next, we evaluated association of AMD with genes in AD-related pathways identified by canonical pathway analysis of AD-associated genes. Significant associations were observed with multiple previously identified AMD risk loci and 2 novel genes: HGS (peak SNP rs8070488, MAF= 0.23, OR= 0.91, p= 7.52× 10^-5), which plays a role in the clathrin-mediated endocytosis signaling pathway, and TNF (peak SNP rs2071590, MAF= 0.34, OR= 0.89, p= 1.17× 10^-5), which is a member of the atherosclerosis signaling and the LXR/RXR activation pathways. Our results suggest that AMD and AD share genetic mechanisms.