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Meta-Analysis
. 2013 Feb 1;54(2):1260-7.
doi: 10.1167/iovs.12-10463.

Identification of a Candidate Gene for Astigmatism

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Free PMC article
Meta-Analysis

Identification of a Candidate Gene for Astigmatism

Margarida C Lopes et al. Invest Ophthalmol Vis Sci. .
Free PMC article

Abstract

Purpose: Astigmatism is a common refractive error that reduces vision, where the curvature and refractive power of the cornea in one meridian are less than those of the perpendicular axis. It is a complex trait likely to be influenced by both genetic and environmental factors. Twin studies of astigmatism have found approximately 60% of phenotypic variance is explained by genetic factors. This study aimed to identify susceptibility loci for astigmatism.

Methods: We performed a meta-analysis of seven genome-wide association studies that included 22,100 individuals of European descent, where astigmatism was defined as the number of diopters of cylinder prescription, using fixed effect inverse variance-weighted methods.

Results: A susceptibility locus was identified with lead single nucleotide polymorphism rs3771395 on chromosome 2p13.3 (meta-analysis, P = 1.97 × 10(-7)) in the VAX2 gene. VAX2 plays an important role in the development of the dorsoventral axis of the eye. Animal studies have shown a gradient in astigmatism along the vertical plane, with corresponding changes in refraction, particularly in the ventral field.

Conclusions: This finding advances the understanding of refractive error, and provides new potential pathways to be evaluated with regard to the development of astigmatism.

Conflict of interest statement

Disclosure: M.C. Lopes, None; P.G. Hysi, None; V.J.M. Verhoeven, None; S. Macgregor, None; A.W. Hewitt, None; G.W. Montgomery, None; P. Cumberland, None; J.R. Vingerling, None; T.L. Young, None; C.M. van Duijn, None; B. Oostra, None; A.G. Uitterlinden, None; J.S. Rahi, None; D.A. Mackey, None; C.C.W. Klaver, None; T. Andrew, None; C.J. Hammond, None

Figures

Figure 1.
Figure 1.
Manhattan plot of 2.8 million single nucleotide polymorphisms (SNPs) for a meta-analysis of seven cohorts for astigmatism. The −log10 P values are plotted against position in each chromosome. Chromosomes are shown in alternating contrasts for clarity. The strongest association is on chromosome 2.
Figure 2.
Figure 2.
Regional association plot for the 2p13.3 (VAX2) risk loci region. Meta-analysis –log P values were plotted against the chromosomal map position. The color of each SNP reflects its r2 value, with the top SNP (blue and genotyped across all cohorts), changing from gray to yellow, orange, and red with increasing r2 value. The lead SNP is not in LD with any of the surrounding SNPs in the region. Estimated McVean's fine-scale recombination rates (from HapMap Phase II) are plotted in light blue. Gene annotations were adapted from the University of California at Santa Cruz genome browser.
Figure 3.
Figure 3.
Forest plot showing the beta coefficients (effect size) for the top associated SNP rs3771395 in the various populations studied. Pooled data are represented as a diamond. Vertical line (beta = 0) indicates no association with astigmatism.

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