@article{304832a7576a4f928c6e14b0bfe55369,
title = "Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration",
abstract = "Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. We conducted a genome-wide association study in a series of families enriched for AMD and completed a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case-control cohort. We tested the top findings for replication in 1896 cases and 1866 controls and identified two novel genetic protective factors for AMD. In addition to the complement factor H (CFH) (P=2.3 × 10-64) and age-related maculopathy susceptibility 2 (ARMS2) (P=1.2 × 10 -60) loci, we observed a protective effect at rs429608, an intronic SNP in SKIV2L (P5.3 × 10-15), a gene near the complement component 2 (C2)/complement factor B (BF) locus, that indicates the protective effect may be mediated by variants other than the C2/BF variants previously studied. Haplotype analysis at this locus identified three protective haplotypes defined by the rs429608 protective allele. We also identified a new potentially protective effect at rs2679798 in MYRIP (P=2.9 × 10-4), a gene involved in retinal pigment epithelium melanosome trafficking. Interestingly, MYRIP was initially identified in the family-based scan and was confirmed in the case-control set. From these efforts, we report the identification of two novel protective factors for AMD and confirm the previously known associations at CFH, ARMS2 and C3.",
keywords = "association testing, macular degeneration, melanosome trafficking",
author = "Kopplin, {L. J.} and Igo, {R. P.} and Y. Wang and Sivakumaran, {T. A.} and Hagstrom, {S. A.} and Peachey, {N. S.} and Francis, {P. J.} and Klein, {M. L.} and Sangiovanni, {J. P.} and Chew, {E. Y.} and Pauer, {G. J.T.} and Sturgill, {G. M.} and T. Joshi and L. Tian and Q. Xi and Henning, {A. K.} and Lee, {K. E.} and R. Klein and Klein, {B. E.K.} and Iyengar, {S. K.}",
note = "Funding Information: This study was supported by the NIH grants EY015810, U10EY06594, EY015286, EY13438 and EY10605 from the National Eye Institute, training grant T32 EY07157 to the Visual Sciences Training Program and T32 GM07250 to the Case Medical Scientist Training Program; US Public Health Service research grants GM28356, from the National Institute of General Medical Sciences; and by Senior Scientific Investigator Awards from Research to Prevent Blindness (Dr R Klein and Dr B Klein), The Foundation Fighting Blindness, Columbia, MD (Dr PJ Francis); the Macular Degeneration Center Research Fund and the Goodall Macular Degeneration Fund, Casey Eye Institute (Dr ML Klein), Research to Prevent Blindness, New York, NY (unrestricted grants to Casey Eye Institute and a Career Development Award to Dr PJ Francis) and unrestricted awards from Research to Prevent Blindness (Department of Ophthalmology, Case Western Reserve University (CWRU) School of Medicine and Cleveland Clinic Lerner College of Medicine of CWRU), a VA Merit Review and a Center Grant from Foundation Fighting Blindness. This study was also supported by the Gene Expression and Genotyping Facility of the Comprehensive Cancer Center at CWRU and University Hospitals of Cleveland (P30CA43703) and the Genotyping Core Facility at CWRU. The results of this paper were obtained by using the software package S.A.G.E., which is supported by a US Public Health Service Resource Grant (RR03655) from the National Center for Research Resources. This publication was made possible by the CWRU/Cleveland Clinic CTSA Grant Number UL1 RR024989 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.",
year = "2010",
month = dec,
doi = "10.1038/gene.2010.39",
language = "English (US)",
volume = "11",
pages = "609--621",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "8",
}