TY - JOUR
T1 - A genome-wide association study of corneal astigmatism
T2 - The CREAM Consortium
AU - CREAM Consortium
AU - Shah, Rupal L
AU - Li, Qing
AU - Zhao, Wanting
AU - Tedja, Milly S
AU - Tideman, J Willem L
AU - Khawaja, Anthony P
AU - Fan, Qiao
AU - Yazar, Seyhan
AU - Williams, Katie M
AU - Verhoeven, Virginie J M
AU - Xie, Jing
AU - Wang, Ya Xing
AU - Hess, Moritz
AU - Nickels, Stefan
AU - Lackner, Karl J
AU - Pärssinen, Olavi
AU - Wedenoja, Juho
AU - Biino, Ginevra
AU - Concas, Maria Pina
AU - Uitterlinden, André
AU - Rivadeneira, Fernando
AU - Jaddoe, Vincent W V
AU - Hysi, Pirro G
AU - Sim, Xueling
AU - Tan, Nicholas
AU - Tham, Yih-Chung
AU - Sensaki, Sonoko
AU - Hofman, Albert
AU - Vingerling, Johannes R
AU - Jonas, Jost B
AU - Mitchell, Paul
AU - Hammond, Christopher J
AU - Höhn, René
AU - Baird, Paul N
AU - Wong, Tien-Yin
AU - Cheng, Chinfsg-Yu
AU - Teo, Yik Ying
AU - Mackey, David A
AU - Williams, Cathy
AU - Saw, Seang-Mei
AU - Klaver, Caroline C W
AU - Guggenheim, Jeremy A
AU - Bailey-Wilson, Joan E
PY - 2018/2/5
Y1 - 2018/2/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85041422197&partnerID=8YFLogxK
M3 - Article
C2 - 29422769
AN - SCOPUS:85041422197
SN - 1090-0535
VL - 24
SP - 127
EP - 142
JO - Molecular Vision
JF - Molecular Vision
ER -