Journal ArticleDOI
Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma.
Gudmar Thorleifsson,Kristinn P. Magnusson,Patrick Sulem,G. Bragi Walters,Daniel F. Gudbjartsson,Hreinn Stefansson,Thorlakur Jonsson,Adalbjorg Jonasdottir,Aslaug Jonasdottir,Gerdur Stefansdottir,Gisli Masson,Gudmundur A. Hardarson,H. Petursson,Arsaell Arnarsson,Mehdi Motallebipour,Ola Wallerman,Claes Wadelius,Jeffrey R. Gulcher,Unnur Thorsteinsdottir,Augustine Kong,Fridbert Jonasson,Kari Stefansson +21 more
TLDR
Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association with glaucoma, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS).Abstract:
Glaucoma is a leading cause of irreversible blindness A genome-wide search yielded multiple single-nucleotide polymorphisms (SNPs) in the 15q241 region associated with glaucoma Further investigation revealed that the association is confined to exfoliation glaucoma (XFG) Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS) About 25% of the general population is homozygous for the highest-risk haplotype, and their risk of suffering from XFG is more than 100 times that of individuals carrying only low-risk haplotypes The population-attributable risk is more than 99% The product of LOXL1 catalyzes the formation of elastin fibers found to be a major component of the lesions in XFGread more
Citations
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Journal ArticleDOI
Primary open-angle glaucoma genes.
TL;DR: Genes that control the magnitude of important quantitative features of glaucoma that may also be important risk factors for POAG, such as central corneal thickness are identified using quantitative traits approaches.
Book ChapterDOI
Astrocytes in glaucomatous optic neuropathy
TL;DR: The data suggests that the creation of a non-supportive environment for the survival of RGC axons through remodeling of the ONH by reactive astrocytes leads to progression of glaucomatous optic neuropathy.
Journal ArticleDOI
Transforming Growth Factor–β Induces Extracellular Matrix Protein Cross-Linking Lysyl Oxidase (LOX) Genes in Human Trabecular Meshwork Cells
TL;DR: Increased LOX activity may be at least partially responsible for TGFβ-mediated IOP elevation and increased aqueous humor outflow resistance, suggesting complex regulation of these important extracellular matrix cross-linking enzymes.
Journal ArticleDOI
What Can Genome-Wide Association Studies Tell Us about the Genetics of Common Disease?
TL;DR: Although the truth of the common disease / common variant hypothesis remains undecided, recent successes suggest that there are many more common genetic disease-associated variants, requiring larger studies to be identified.
Journal ArticleDOI
Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia
Pirro G. Hysi,Pirro G. Hysi,Hélène Choquet,Anthony P Khawaja,Anthony P Khawaja,Robert Wojciechowski,Milly S. Tedja,Jie Yin,Mark James Simcoe,Karina Patasova,Omar A. Mahroo,Omar A. Mahroo,Khanh K. Thai,Phillippa M. Cumberland,Ronald B. Melles,Virginie J. M. Verhoeven,Veronique Vitart,Ayellet V. Segrè,Richard A. Stone,Nicholas J. Wareham,Alex W. Hewitt,David A. Mackey,David A. Mackey,Caroline C W Klaver,Stuart MacGregor,Myopia,Peng T. Khaw,Paul J. Foster,UK Eye,Jeremy A. Guggenheim,Jugnoo S Rahi,Eric Jorgenson,Christopher J Hammond +32 more
TL;DR: A meta-analysis of genome-wide association studies of 542,934 individuals identifies 336 novel loci associated with refractive error and implicates eye development, circadian rhythm and pigmentation pathways in controlling myopia.
References
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Nathan Mantel,William Haenszel +1 more
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Journal ArticleDOI
The definition and classification of glaucoma in prevalence surveys
TL;DR: This review describes a scheme for diagnosis of glaucoma in population based prevalence surveys that makes provision for diagnosing glauca in eyes with severe visual loss where formal field testing is impractical, and for blind eyes in which the optic disc cannot be seen because of media opacities.
Journal ArticleDOI
Identification of a Gene That Causes Primary Open Angle Glaucoma
Edwin M. Stone,John H. Fingert,Wallace L.M. Alward,Thai Nguyen,Jon R. Polansky,Sara L.F. Sunden,Darryl Y. Nishimura,Abbot F. Clark,Arne M. Nystuen,Brian E. Nichols,David A. Mackey,Robert Ritch,Jeffrey W. Kalenak,E. Randy Craven,Val C. Sheffield +14 more
TL;DR: A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping and will aid in early diagnosis of glaucoma.