A genome-wide association study of corneal astigmatism

• Verfasst von: Shah, Rupal [VerfasserIn]
• Verfasst von: Jonas, Jost B. [VerfasserIn]
• Titel: A genome-wide association study of corneal astigmatism
• Titelzusatz: the CREAM Consortium
• Verf.angabe: Rupal L. Shah, Qing Li, Wanting Zhao, Milly S. Tedja, J. Willem L. Tideman, Anthony P. Khawaja, Qiao Fan, Seyhan Yazar, Katie M. Williams, Virginie J. M. Verhoeven, Jing Xie, Ya Xing Wang, Moritz Hess, Stefan Nickels, Karl J. Lackner, Olavi Pärssinen, Juho Wedenoja, Ginevra Biino, Maria Pina Concas, André Uitterlinden, Fernando Rivadeneira, Vincent W. V. Jaddoe, Pirro G. Hysi, Xueling Sim, Nicholas Tan, Yih-Chung Tham, Sonoko Sensaki, Albert Hofman, Johannes R. Vingerling, Jost B. Jonas, Paul Mitchell, Christopher J. Hammond, René Höhn, Paul N. Baird, Tien-Yin Wong, Chinfsg-Yu Cheng, Yik Ying Teo, David A. Mackey, Cathy Williams, Seang-Mei Saw, Caroline C. W. Klaver, Jeremy A. Guggenheim, Joan E. Bailey-Wilson, CREAM Consortium
• E-Jahr: 2018
• Jahr: 5 February 2018
• Umfang: 16 S.
• Fussnoten: Gesehen am 05.05.2020
• Titel Quelle: Enthalten in: Molecular vision
• Ort Quelle: [Erscheinungsort nicht ermittelbar] : [Verlag nicht ermittelbar], 1995
• Jahr Quelle: 2018
• Band/Heft Quelle: 24(2018), Seite 127-142
• ISSN Quelle: 1090-0535
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Acid Phosphatase
• Sach-SW: Asian Continental Ancestry Group
• Sach-SW: Astigmatism
• Sach-SW: Claudins
• Sach-SW: Cohort Studies
• Sach-SW: Cornea
• Sach-SW: Corneal Diseases
• Sach-SW: European Continental Ancestry Group
• Sach-SW: Gene Expression
• Sach-SW: Genetic Predisposition to Disease
• Sach-SW: Genome-Wide Association Study
• Sach-SW: Humans
• Sach-SW: Intracellular Signaling Peptides and Proteins
• Sach-SW: Odds Ratio
• Sach-SW: Polymorphism, Single Nucleotide
• Sach-SW: Receptor, Platelet-Derived Growth Factor alpha
• Sach-SW: Software
• K10plus-PPN: 1697204546

Abstract

Purpose: To identify genes and genetic markers associated with corneal astigmatism. - Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. - Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). - Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.