Abstract
Central corneal thickness (CCT) is one of the most heritable human traits, with broad-sense heritability estimates ranging between 0.68 to 0.95. Despite the high heritability and numerous previous association studies, only 8.5% of CCT variance is currently explained. Here, we report the results of a multiethnic meta-analysis of available genome-wide association studies in which we find association between CCT and 98 genomic loci, of which 41 are novel. Among these loci, 20 were significantly associated with keratoconus, and one (RAPSN rs3740685) was significantly associated with glaucoma after Bonferroni correction. Two-sample Mendelian randomization analysis suggests that thinner CCT does not causally increase the risk of primary open-angle glaucoma. This large CCT study explains up to 14.2% of CCT variance and increases substantially our understanding of the etiology of CCT variation. This may open new avenues of investigation into human ocular traits and their relationship to the risk of vision disorders.
Highlights
Central corneal thickness (CCT) is one of the most heritable human traits, with broad-sense heritability estimates ranging between 0.68 to 0.95
Our GERA sample consisted of 18,129 individuals from four ethnic groups (79.9% non-Hispanic white, 7.5% Hispanic/Latino, 8.4% East Asian, and 4.2% African American) with a measured CCT (Table 1)
As previous studies have reported that CCT is significantly lower in eyes with keratoconus compared to normal eyes[1,22], we evaluated the effect estimates of the 98 CCT-SNPs identified in the current study (74 from the combined meta-analysis + 24 from the conditional and joint association analysis (COJO) analysis) between CCT and keratoconus in GERA
Summary
Central corneal thickness (CCT) is one of the most heritable human traits, with broad-sense heritability estimates ranging between 0.68 to 0.95. Two-sample Mendelian randomization analysis suggests that thinner CCT does not causally increase the risk of primary open-angle glaucoma. This large CCT study explains up to 14.2% of CCT variance and increases substantially our understanding of the etiology of CCT variation. This may open new avenues of investigation into human ocular traits and their relationship to the risk of vision disorders. Iglesias et al.[14] reported 44 CCT-genomic regions in a cross-ancestry meta-analysis, including 19 novel loci awaiting independent replication These 44 CCT-loci account for ~8.5% of the variance for this ocular trait.
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