PURPOSE: The purpose of this study was to identify genetic contributions to primary open-angle glaucoma (POAG) through investigations of two quantitative components of the POAG phenotype. METHODS: Genome-wide multipoint variance-components linkage analyses of maximum recorded intraocular pressure (IOP) and maximum vertical cup-to-disc ratio were conducted on data from a single, large Australian POAG pedigree that has been found to segregate the myocilin Q368X mutation in some individuals. RESULTS: Multipoint linkage analysis of maximum recorded IOP produced a peak LOD score of 3.3 (P = 0.00015) near marker D10S537 on 10q22, whereas the maximum cup-to-disc ratio produced a peak LOD score of 2.3 (P = 0.00056) near markers D1S197 to D1S220 on 1p32. Inclusion of the myocilin Q368X mutation as a covariate provided evidence of an interaction between this mutation and the IOP and cup-to-disc ratio loci. CONCLUSIONS: Significant linkage has been identified for maximum IOP and suggestive linkage for vertical cup-to-disc ratio. Identification of genes contributing to the variance of these traits will enhance understanding of the pathophysiology of POAG as a whole.
PURPOSE: The purpose of this study was to identify genetic contributions to primary open-angle glaucoma (POAG) through investigations of two quantitative components of the POAG phenotype. METHODS: Genome-wide multipoint variance-components linkage analyses of maximum recorded intraocular pressure (IOP) and maximum vertical cup-to-disc ratio were conducted on data from a single, large Australian POAG pedigree that has been found to segregate the myocilinQ368X mutation in some individuals. RESULTS: Multipoint linkage analysis of maximum recorded IOP produced a peak LOD score of 3.3 (P = 0.00015) near marker D10S537 on 10q22, whereas the maximum cup-to-disc ratio produced a peak LOD score of 2.3 (P = 0.00056) near markers D1S197 to D1S220 on 1p32. Inclusion of the myocilinQ368X mutation as a covariate provided evidence of an interaction between this mutation and the IOP and cup-to-disc ratio loci. CONCLUSIONS: Significant linkage has been identified for maximum IOP and suggestive linkage for vertical cup-to-disc ratio. Identification of genes contributing to the variance of these traits will enhance understanding of the pathophysiology of POAG as a whole.
Authors: Jac Charlesworth; Patricia L Kramer; Tom Dyer; Victor Diego; John R Samples; Jamie E Craig; David A Mackey; Alex W Hewitt; John Blangero; Mary K Wirtz Journal: Invest Ophthalmol Vis Sci Date: 2010-03-17 Impact factor: 4.799
Authors: Fei Chen; Alison P Klein; Barbara E K Klein; Kristine E Lee; Barbara Truitt; Ronald Klein; Sudha K Iyengar; Priya Duggal Journal: Invest Ophthalmol Vis Sci Date: 2014-12-18 Impact factor: 4.799
Authors: Francis Carbonaro; Toby Andrew; David A Mackey; Terri L Young; Tim D Spector; Christopher J Hammond Journal: Invest Ophthalmol Vis Sci Date: 2009-05-06 Impact factor: 4.799
Authors: Leonieke M E van Koolwijk; Wishal D Ramdas; M Kamran Ikram; Nomdo M Jansonius; Francesca Pasutto; Pirro G Hysi; Stuart Macgregor; Sarah F Janssen; Alex W Hewitt; Ananth C Viswanathan; Jacoline B ten Brink; S Mohsen Hosseini; Najaf Amin; Dominiek D G Despriet; Jacqueline J M Willemse-Assink; Rogier Kramer; Fernando Rivadeneira; Maksim Struchalin; Yurii S Aulchenko; Nicole Weisschuh; Matthias Zenkel; Christian Y Mardin; Eugen Gramer; Ulrich Welge-Lüssen; Grant W Montgomery; Francis Carbonaro; Terri L Young; Céline Bellenguez; Peter McGuffin; Paul J Foster; Fotis Topouzis; Paul Mitchell; Jie Jin Wang; Tien Y Wong; Monika A Czudowska; Albert Hofman; Andre G Uitterlinden; Roger C W Wolfs; Paulus T V M de Jong; Ben A Oostra; Andrew D Paterson; David A Mackey; Arthur A B Bergen; André Reis; Christopher J Hammond; Johannes R Vingerling; Hans G Lemij; Caroline C W Klaver; Cornelia M van Duijn Journal: PLoS Genet Date: 2012-05-03 Impact factor: 5.917