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Title | Search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Logue MW, Schu M, Vardarajan BN, Farrell J, Lunetta KL, Jun G, Baldwin CT, Deangelis MM, Farrer LA |
Journal | Neurobiol Aging |
Volume | 35 |
Issue | 6 |
Pagination | 1510.e7-18 |
Date Published | 2014 Jun |
ISSN | 1558-1497 |
Keywords | Alzheimer Disease, ATP-Binding Cassette Transporters, Chromosomes, Human, Pair 7, Clathrin, Endocytosis, Endosomal Sorting Complexes Required for Transport, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Macular Degeneration, Membrane Glycoproteins, Phosphoproteins, Receptors, Immunologic, Retinoid X Receptors, Risk, Signal Transduction, Tumor Necrosis Factor-alpha, Wnt Signaling Pathway |
Abstract | 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. |
DOI | 10.1016/j.neurobiolaging.2013.12.007 |
Alternate Journal | Neurobiol. Aging |
PubMed ID | 24439028 |
PubMed Central ID | PMC3961547 |
Grant List | U01-AG032984 / AG / NIA NIH HHS / United States PG30-AG13846 / AG / NIA NIH HHS / United States R01 EY014458 / EY / NEI NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States R01-AG025259 / AG / NIA NIH HHS / United States R01-EY0144581 / EY / NEI NIH HHS / United States R01 AG025259 / AG / NIA NIH HHS / United States |