RESUMEN
The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10-8): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.
Asunto(s)
Distrofia Endotelial de Fuchs/genética , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Curva ROC , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
PURPOSE: To determine the role of the single nucleotide polymorphism (SNP) (rs613872) in the TCF4 gene in Fuchs endothelial corneal dystrophy (FECD) in patients from Iowa. METHODS: A cohort of 82 patients with FECD and 163 normal control subjects from Iowa were genotyped at the SNP rs613872 using a real-time allelic discrimination assay. RESULTS: The frequencies of the alleles of rs613872 were compared between FECD patients and control subjects. A highly significant association (p-value = 2.96 × 10(-10)) was detected between this SNP and FECD. Comparison of the genotypes of SNP rs613872 between FECD patients and control subjects produced a p-value of 2.43 × 10(-10). CONCLUSION: Prior reports have shown that SNP rs613872 in the TCF4 gene is highly associated with FECD. Our study confirms this association and shows that the TCF4 gene has an important role in the pathogenesis of corneal disease in patients from Iowa.