Dataset Information

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

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.

SUBMITTER: Shah RL

PROVIDER: S-EPMC5800430 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

Shah Rupal L RL Li Qing Q Zhao Wanting W Tedja Milly S MS Tideman J Willem L JWL Khawaja Anthony P AP Fan Qiao Q Yazar Seyhan S Williams Katie M KM Verhoeven Virginie J M VJM Xie Jing J Wang Ya Xing YX Hess Moritz M Nickels Stefan S Lackner Karl J KJ Pärssinen Olavi O Wedenoja Juho J Biino Ginevra G Concas Maria Pina MP Uitterlinden André A Rivadeneira Fernando F Jaddoe Vincent W V VWV Hysi Pirro G PG Sim Xueling X Tan Nicholas N Tham Yih-Chung YC Sensaki Sonoko S Hofman Albert A Vingerling Johannes R JR Jonas Jost B JB Mitchell Paul P Hammond Christopher J CJ Höhn René R Baird Paul N PN Wong Tien-Yin TY Cheng Chinfsg-Yu CY Teo Yik Ying YY Mackey David A DA Williams Cathy C Saw Seang-Mei SM Klaver Caroline C W CCW Guggenheim Jeremy A JA Bailey-Wilson Joan E JE

Molecular vision 20180205

<h4>Purpose</h4>To identify genes and genetic markers associated with corneal astigmatism.<h4>Methods</h4>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 ...[more]

PMID: 29422769

Similar Datasets

Project description:BackgroundSurgically induced astigmatism (SIA) was one of the factors that influences the desirable refractive outcome, and it was related to the length, type, location, structure of the incision and to the suture closure technique, etc. The aim was to evaluate the association of corneal histocytological changes with SIA after phacoemulsification.MethodsThe study enrolled 68 cases of cataract patient (68 eyes). Corneal histocytological parameters at corneal incision, central cornea and contralateral incision obtained by confocal microscope through focusing (CMTF) were compared preoperatively and 1 week, 2 weeks, 1 month, 3 months and 6 months postoperatively. These biometric parameters included the endothelial cell density, keratocyte density of posterior stromal layer, and the morphological changes. SIA was calculated by Jaffe's vector analysis.Results1 From preoperatively to 1 week, 2 weeks, 1 month, 3 months and 6 months postoperatively, the endothelail cell density was decreased significantly (p < 0.05). Keratocyte density of posterior stroma layer was increased significantly only at 1 week, 2 weeks, 1 month, 3 months postoperatively (p <0.05), but not statistically significant (p = 0.173) at 6 months postoperatively compared to preoperative values. 2 The histocytological observations indicated that the morphology changed significantly postoperatively at the corneal incision, including the cell absent area, wave-like area, dot-like and mass-like hyperreflection, stripe-like absent area, in the endothelial layer, and the keratocyte activation, microfolds, irregular hyporeflective or hyperreflective belt, and a little dot-like hyperreflection in the posterior stroma layer. 3 The reduction of the endothelial cell density at the corneal incision at 1 week, 2 weeks, 1 month postoperatively, were positively correlated with SIA (P1 week = 0.003, P2 weeks = 0.003, P1 month = 0.032), while others were not associated with SIA statistically.ConclusionsThe reduction of endothelail cell density and the histocytological changes at the corneal incision were associated with SIA. The underlining mechanism needs further study.

Dataset Information

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

Publications

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets