Johanna M Seddon1, Robyn Reynolds, Bernard Rosner. 1. Ophthalmic Epidemiology and Genetics Service, Department of Ophthalmology, Tufts University School of Medicine and Tufts Medical Center, New England Eye Center, Boston, Massachusetts 02111, USA. jseddon@tuftsmedicalcenter.org
Abstract
PURPOSE: To evaluate the relationship between peripheral retinal drusen and reticular pigment changes and genotypes associated with age-related macular degeneration (AMD). METHODS: Using standard protocols, 2103 family members and twins were examined. Clinical and photographic data were graded according to the Clinical Age-Related Maculopathy Grading System (CARMS) as grade 1 (no AMD), grade 2 (small drusen and/or pigment irregularities), grade 3 (intermediate AMD), grade 4 (central or noncentral geographic atrophy), or grade 5 (neovascular disease). Peripheral drusen and reticular pigment were assessed with a standardized examination. Associations between six AMD genetic variants and retinal phenotypes were analyzed. RESULTS: AMD grade was associated with peripheral drusen and reticular pigment (odds ratio [OR] 1.9 for advanced AMD; P<0.001). Both peripheral retinal phenotypes were associated with AMD related genotypes. For CFHY402H, the OR was 2.8 for the CC genotype versus TT (P for trend<0.001, with increase in peripheral drusen with each additional risk [C] allele). Similar results were seen for CFHrs1410996. Reticular pigment was related to CFHY402H, with OR 2.0 for the CC genotype versus TT (P for trend<0.001, for increase in pigment with each risk allele) and to CFHrs1410996 (P for trend=0.006). These findings were not seen for the LOC387715 A69S gene region, CFB, C2, or C3. Among individuals with no or minimal maculopathy, CFH variants were associated with more than a twofold increased risk of drusen and reticular pigment. CONCLUSIONS: Peripheral retinal drusen and reticular pigment are associated with AMD and with CFHY402H and CFHrs1410996 genotypes, adjusting for AMD grade. These phenotypes may be a marker of genetic susceptibility for patients with or without AMD.
PURPOSE: To evaluate the relationship between peripheral retinal drusen and reticular pigment changes and genotypes associated with age-related macular degeneration (AMD). METHODS: Using standard protocols, 2103 family members and twins were examined. Clinical and photographic data were graded according to the Clinical Age-Related Maculopathy Grading System (CARMS) as grade 1 (no AMD), grade 2 (small drusen and/or pigment irregularities), grade 3 (intermediate AMD), grade 4 (central or noncentral geographic atrophy), or grade 5 (neovascular disease). Peripheral drusen and reticular pigment were assessed with a standardized examination. Associations between six AMD genetic variants and retinal phenotypes were analyzed. RESULTS:AMD grade was associated with peripheral drusen and reticular pigment (odds ratio [OR] 1.9 for advanced AMD; P<0.001). Both peripheral retinal phenotypes were associated with AMD related genotypes. For CFHY402H, the OR was 2.8 for the CC genotype versus TT (P for trend<0.001, with increase in peripheral drusen with each additional risk [C] allele). Similar results were seen for CFHrs1410996. Reticular pigment was related to CFHY402H, with OR 2.0 for the CC genotype versus TT (P for trend<0.001, for increase in pigment with each risk allele) and to CFHrs1410996 (P for trend=0.006). These findings were not seen for the LOC387715 A69S gene region, CFB, C2, or C3. Among individuals with no or minimal maculopathy, CFH variants were associated with more than a twofold increased risk of drusen and reticular pigment. CONCLUSIONS: Peripheral retinal drusen and reticular pigment are associated with AMD and with CFHY402H and CFHrs1410996 genotypes, adjusting for AMD grade. These phenotypes may be a marker of genetic susceptibility for patients with or without AMD.
Authors: Robert J Klein; Caroline Zeiss; Emily Y Chew; Jen-Yue Tsai; Richard S Sackler; Chad Haynes; Alice K Henning; John Paul SanGiovanni; Shrikant M Mane; Susan T Mayne; Michael B Bracken; Frederick L Ferris; Jurg Ott; Colin Barnstable; Josephine Hoh Journal: Science Date: 2005-03-10 Impact factor: 47.728
Authors: Julian B Maller; Jesen A Fagerness; Robyn C Reynolds; Benjamin M Neale; Mark J Daly; Johanna M Seddon Journal: Nat Genet Date: 2007-09-02 Impact factor: 38.330
Authors: Julian Maller; Sarah George; Shaun Purcell; Jes Fagerness; David Altshuler; Mark J Daly; Johanna M Seddon Journal: Nat Genet Date: 2006-08-27 Impact factor: 38.330
Authors: Andrew Dewan; Mugen Liu; Stephen Hartman; Samuel Shao-Min Zhang; David T L Liu; Connie Zhao; Pancy O S Tam; Wai Man Chan; Dennis S C Lam; Michael Snyder; Colin Barnstable; Chi Pui Pang; Josephine Hoh Journal: Science Date: 2006-10-19 Impact factor: 47.728
Authors: Zhenglin Yang; Nicola J Camp; Hui Sun; Zongzhong Tong; Daniel Gibbs; D Joshua Cameron; Haoyu Chen; Yu Zhao; Erik Pearson; Xi Li; Jeremy Chien; Andrew Dewan; Jennifer Harmon; Paul S Bernstein; Viji Shridhar; Norman A Zabriskie; Josephine Hoh; Kimberly Howes; Kang Zhang Journal: Science Date: 2006-10-19 Impact factor: 47.728
Authors: Johanna M Seddon; Peter J Francis; Sarah George; Dennis W Schultz; Bernard Rosner; Michael L Klein Journal: JAMA Date: 2007-04-25 Impact factor: 56.272
Authors: Gwenole Quellec; Stephen R Russell; Johanna M Seddon; Robyn Reynolds; Todd Scheetz; Vinit B Mahajan; Edwin M Stone; Michael D Abràmoff Journal: Invest Ophthalmol Vis Sci Date: 2011-11-25 Impact factor: 4.799
Authors: Yi Yu; Robyn Reynolds; Jesen Fagerness; Bernard Rosner; Mark J Daly; Johanna M Seddon Journal: Invest Ophthalmol Vis Sci Date: 2011-06-28 Impact factor: 4.799
Authors: Nathan G Lambert; Hanan ElShelmani; Malkit K Singh; Fiona C Mansergh; Michael A Wride; Maximilian Padilla; David Keegan; Ruth E Hogg; Balamurali K Ambati Journal: Prog Retin Eye Res Date: 2016-05-06 Impact factor: 21.198