title: Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.
abstract: To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive Suite 1200, Baltimore, MD, 21224, USA.
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mesh_terms: D000328:Adult; D000367:Age Factors; D044466:Asian People; D001251:Astigmatism / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D044465:White People
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D005819:Genetic Markers; D006609:High Mobility Group Proteins; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C558851:TOX protein, human