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
Tissue-Specific Genetic Control of Splicing: Implications for the Study of Complex Traits
Erin L. Heinzen,Dongliang Ge,Kenneth D. Cronin,Jessica M. Maia,Kevin V. Shianna,Willow N Gabriel,Kathleen A. Welsh-Bohmer,Christine M. Hulette,Thomas N. Denny,David Goldstein +9 more
TL;DR: The first genome-wide screen for SNPs that associate with alternative splicing and gene expression in human primary cells, evaluating 93 autopsy-collected cortical brain tissue samples with no defined neuropsychiatric condition and 80 peripheral blood mononucleated cell samples collected from living healthy donors, suggests that splicing effects may be of more phenotypic significance than overall gene expression changes.
Journal ArticleDOI
Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma.
TL;DR: This review summarizes the current literature on trabecular ECM as well as the development and function of the TM and the growing number of mutations that have been identified in ECM genes and genes that modulate ECM in humans with glaucoma are documented.
Journal ArticleDOI
Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma
Janey L. Wiggs,Brian L. Yaspan,Michael A. Hauser,Jae H. Kang,R. Rand Allingham,Lana M. Olson,Wael Abdrabou,Baojian Fan,Dan Y. Wang,Wendy Brodeur,Donald L. Budenz,Joseph Caprioli,Andrew Crenshaw,Kristy Crooks,E. DelBono,Kimberly F. Doheny,David S. Friedman,Douglas E. Gaasterland,Terry Gaasterland,Cathy C. Laurie,Richard K. Lee,Paul R. Lichter,Stephanie Loomis,Yutao Liu,Felipe A. Medeiros,Catherine A. McCarty,Daniel B. Mirel,Sayoko E. Moroi,David C. Musch,Anthony Realini,Frank W. Rozsa,Joel S. Schuman,Kathleen M. Scott,Kuldev Singh,Joshua D. Stein,Edward H. Trager,Paul C. VanVeldhuisen,Douglas Vollrath,Gadi Wollstein,Sachiko Yoneyama,Kang Zhang,Robert N. Weinreb,Jason Ernst,Manolis Kellis,Tomohiro Masuda,Donald J. Zack,Julia E. Richards,Margaret A. Pericak-Vance,Louis R. Pasquale,Jonathan L. Haines +49 more
TL;DR: The authors performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal pressure (NPG) defined by intraocular pressure (IOP) less than 22 mmHg subgroup analysis.
Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma
Janey L. Wiggs,Brian L. Yaspan,Michael A. Hauser,Jae H. Kang,R. Rand Allingham,Lana M. Olson,Wael Abdrabou,Baojian Fan,Dan Y. Wang,Wendy Brodeur,Donald L. Budenz,Joseph Caprioli,Andrew Crenshaw,Kristy Crooks,E. DelBono,Kimberly F. Doheny,David S. Friedman,Douglas E. Gaasterland,Terry Gaasterland,Cathy C. Laurie,Richard K. Lee,Paul R. Lichter,Stephanie Loomis,Yutao Liu,Felipe A. Medeiros,Catherine A. McCarty,Daniel B. Mirel,Sayoko E. Moroi,David C. Musch,Anthony Realini,Frank W. Rozsa,Joel S. Schuman,Kathleen M. Scott,Kuldev Singh,Joshua D. Stein,Edward H. Trager,Paul C. VanVeldhuisen,Douglas Vollrath,Gadi Wollstein,Sachiko Yoneyama,Kang Zhang,Robert N. Weinreb,Jason Ernst,Manolis Kellis,Tomohiro Masuda,Donald J. Zack,Julia E. Richards,Margaret A. Pericak-Vance,Louis R. Pasquale,Jonathan L. Haines +49 more
TL;DR: It is suggested that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma, and genomic pathway analysis showed an association between the T GF-beta pathway and NPG.
Journal ArticleDOI
Genetics of glaucoma.
TL;DR: Genetic and genomic studies are defining important biological pathways and processes that contribute to disease pathogenesis, including genome-wide association studies (GWAS) for common adult-onset glaucoma.
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.