Genetic analysis of TGFBI variants in the Taiwanese population: from granular corneal dystrophy type 1 to a broader phenotypic spectrum.

objectivesGranular corneal dystrophy type 1 (GCD1) is an autosomal dominant hereditary corneal disorder caused by pathogenic variants in the TGFBI gene. However, the population distribution of TGFBI (Transforming Growth Factor Beta Induced) variants in Taiwan remains incompletely characterized. This study aimed to investigate the spectrum and population frequency of coding variants in TGFBI within the Taiwanese population using genomic data from the Taiwan Biobank.

methodsWhole genome sequencing (WGS) data from Taiwan Biobank participants were analyzed to identify exonic single-nucleotide polymorphisms (SNPs) causing coding sequence alterations in the TGFBI gene. Allele frequencies were estimated and compared against probe-based SNP array data and East Asian population reference data from the 1000 Genomes Project. Phenotypic information was obtained from self-reported questionnaire data available within the Taiwan Biobank.

resultsA total of 22 exonic SNPs causing coding sequence alterations were identified in TGFBI. One variant, rs121909212 (p.P501T) was observed at a notably higher allele frequency (0.003) compared to other identified variants. The estimated allele frequency of rs121909212 in the Taiwanese population was approximately 0.003, which is comparable to the frequency reported in the Japanese population. Furthermore, WGS-based allele frequency estimates showed greater consistency with reference population data than SNP array-based genotyping.

conclusionsOur findings provide a population-level overview of TGFBI coding variation in the Taiwanese population and identify rs121909212 as a rare variant prevalent in East Asian populations. The study also highlights the utility of WGS for accurately characterizing rare pathogenic variants in population-scale genomic datasets.