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

Publication ,  Journal Article
Shah, RL; Li, Q; Zhao, W; Tedja, MS; Tideman, JWL; Khawaja, AP; Fan, Q; Yazar, S; Williams, KM; Verhoeven, VJM; Xie, J; Wang, YX; Hess, M ...
Published in: Mol Vis
2018

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.

Duke Scholars

Published In

Mol Vis

EISSN

1090-0535

Publication Date

2018

Volume

24

Start / End Page

127 / 142

Location

United States

Related Subject Headings

  • White People
  • Software
  • Receptor, Platelet-Derived Growth Factor alpha
  • Polymorphism, Single Nucleotide
  • Ophthalmology & Optometry
  • Odds Ratio
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shah, R. L., Li, Q., Zhao, W., Tedja, M. S., Tideman, J. W. L., Khawaja, A. P., … CREAM Consortium, . (2018). A genome-wide association study of corneal astigmatism: The CREAM Consortium. Mol Vis, 24, 127–142.
Shah, Rupal L., Qing Li, Wanting Zhao, Milly S. Tedja, J Willem L. Tideman, Anthony P. Khawaja, Qiao Fan, et al. “A genome-wide association study of corneal astigmatism: The CREAM Consortium.Mol Vis 24 (2018): 127–42.
Shah RL, Li Q, Zhao W, Tedja MS, Tideman JWL, Khawaja AP, et al. A genome-wide association study of corneal astigmatism: The CREAM Consortium. Mol Vis. 2018;24:127–42.
Shah, Rupal L., et al. “A genome-wide association study of corneal astigmatism: The CREAM Consortium.Mol Vis, vol. 24, 2018, pp. 127–42.
Shah RL, Li Q, Zhao W, Tedja MS, Tideman JWL, Khawaja AP, Fan Q, Yazar S, Williams KM, Verhoeven VJM, Xie J, Wang YX, Hess M, Nickels S, Lackner KJ, Pärssinen O, Wedenoja J, Biino G, Concas MP, Uitterlinden A, Rivadeneira F, Jaddoe VWV, Hysi PG, Sim X, Tan N, Tham Y-C, Sensaki S, Hofman A, Vingerling JR, Jonas JB, Mitchell P, Hammond CJ, Höhn R, Baird PN, Wong T-Y, Cheng C-Y, Teo YY, Mackey DA, Williams C, Saw S-M, Klaver CCW, Guggenheim JA, Bailey-Wilson JE, CREAM Consortium. A genome-wide association study of corneal astigmatism: The CREAM Consortium. Mol Vis. 2018;24:127–142.

Published In

Mol Vis

EISSN

1090-0535

Publication Date

2018

Volume

24

Start / End Page

127 / 142

Location

United States

Related Subject Headings

  • White People
  • Software
  • Receptor, Platelet-Derived Growth Factor alpha
  • Polymorphism, Single Nucleotide
  • Ophthalmology & Optometry
  • Odds Ratio
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease