Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration
| Autor: | Caroline C W Klaver, Donald J. Zack, Paul N. Baird, Rando Allikmets, Tushar Bhangale, Andrea J. Richardson, Gabriëlle H.S. Buitendijk, Joanna E. Merriam, R. Theodore Smith, André G. Uitterlinden, Cornelia M. van Duijn, Kimberly A Chin, Nicholas Katsanis, Eric H Souied, Luba D Robman, Nicolas Leveziel, Robyn Reynolds, Gudmar Thorleifsson, Johannes R. Vingerling, Perciliz L. Tan, Aaron Y. Lee, Lucia Sobrin, Phil Lee, Soumya Raychaudhuri, Yi Yu, Betsy Campochiaro, Kari Stefansson, Mark J. Daly, Ward Ortmann, Usha Chakravarthy, Peter A. Campochiaro, Jesen Fagerness, Gaetano R. Barile, Johanna M. Seddon, Milam A. Brantley, Omar Gustafsson, Unnur Thorsteinsdottir, Evangelos Evangelou, Ruth E Hogg, Timothy W. Behrens, Stephan Ripke, Robyn H. Guymer, Haraldur Sigurdsson, Robert R. Graham, John P. A. Ioannidis |
|---|---|
| Přispěvatelé: | Biochemistry, Ophthalmology, Internal Medicine, Epidemiology |
| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
Male haplotype Genome-wide association study susceptibility Cohort Studies Macular Degeneration angiogenesis 0302 clinical medicine Genome-Wide Association Study European Continental Ancestry Group/genetics Genetics (clinical) risk Genetics 0303 health sciences Association Studies Articles General Medicine Protein-Tyrosine Kinases Protein-Tyrosine Kinases/*genetics Genetic Variation Neoplasm Proteins 3. Good health genetic-association loci Female metaanalysis Genotype Vascular Endothelial Growth Factor A/*genetics Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide White People 03 medical and health sciences complement factor-h Genetic variation Genetic predisposition Humans Allele 1000 Genomes Project Neoplasm Proteins/*genetics Molecular Biology 030304 developmental biology Genetic association disease Macular Degeneration/*genetics Haplotype eye diseases Case-Control Studies 030221 ophthalmology & optometry genome-wide association Collagen Type X/*genetics Collagen Type X |
| Zdroj: | Human Molecular Genetics, 20(18), 3699-3709. Oxford University Press Human Molecular Genetics |
| ISSN: | 0964-6906 |
| Popis: | Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P = 1.1 x 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 x 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD. Hum Mol Genet |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|