http://repub.eur.nl/res/aut/40653/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39576/ 2013-02-01T00:00:00Z 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. http://repub.eur.nl/res/pub/28307/ 2010-10-01T00:00:00Z Myopia and hyperopia are at opposite ends of the continuum of refraction, the measure of the eyeĝ€2s ability to focus light, which is an important cause of visual impairment (when aberrant) and is a highly heritable trait. We conducted a genome-wide association study for refractive error in 4,270 individuals from the TwinsUK cohort. We identified SNPs on 15q25 associated with refractive error (rs8027411, P = 7.91 × 10-8). We replicated this association in six adult cohorts of European ancestry with a combined 13,414 individuals (combined P = 2.07 × 10-9). This locus overlaps the transcription initiation site of RASGRF1, which is highly expressed in neurons and retina and has previously been implicated in retinal function and memory consolidation. Rasgrf1-/-mice show a heavier average crystalline lens (P = 0.001). The identification of a susceptibility locus for refractive error on 15q25 will be important in characterizing the molecular mechanism responsible for the most common cause of visual impairment.