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PURPOSE: To study the genetic risk factors of Fuchs endothelial corneal dystrophy (FECD) in the Finnish population using hospital-based and large biobank cohorts.METHODS: We genotyped a cohort of 107 Finnish patients with FECD for the primary associated genetic risk factor, the TCF4 (CTG) expansion, and studied their clinical phenotype. For 18 TCF4 (CTG) patients, we performed exome-based candidate gene analysis. We also utilised FinnGen biobank-based samples to perform a genome-wide association study (GWAS).RESULTS: In the cohort, 83% (89/107) carried one allele with the TCF4 (CTG) expansion. Those without the expansion were younger at enrolment and at the time of first keratoplasty (p = 0.011, p = 0.044, respectively). A genome-wide association study of 892 patients and 497 827 controls identified a lead variant rs11659764 (AF = 2.3%, OR = 8.2, p = 2.9 × 10). Genotyping showed that 89% of TCF4 (CTG) carriers had the associated TA genotype rather than the TT genotype, whereas none of the TCF4 (CTG) carriers did. Exome-based analyses of the 18 TCF4 (CTG) carriers identified a candidate gene variant, AGBL1 c.901 + 2 T>G in one patient.CONCLUSION: In Finland, the TCF4 (CTG) expansion is a significant risk factor for FECD. A nearby single-nucleotide polymorphism (SNP) was found to perform well as a surrogate for genotyping. However, not all patients carried the expanded repeat, and a variant in a previously associated gene was observed in a single patient. Further research is needed to investigate the origins of FECD in individuals without the repeat expansion.