RESUMO
PURPOSE: Genomic studies have demonstrated the necessity of ethnicity-specific population data to ascertain variant pathogenicity for disease diagnosis and treatment. This study examined the carrier prevalence of treatable inherited disorders (TIDs), where early diagnosis of at-risk offspring can significantly improve clinical outcomes. METHODS: Existing exome/ genome sequencing data of 831 Singaporeans were aggregated and examined for disease causing variants in 104 genes associated with 80 TIDs. RESULTS: Among the 831 Singaporean participants, genomic variant filtering and analysis identified 1 in 18 individuals (6%) to be carriers amongst one of 13 TIDs. Citrin deficiency and Wilson disease had the highest carrier frequency of 1 in 41, and 1 in 103 individuals, respectively. The pathogenic variants associated with citrin deficiency were 24 times more prevalent in our local cohorts when compared to Western cohorts. CONCLUSION: This study demonstrates the value of a population specific genomic database to determine true disease prevalence and has enabled the discovery of carrier frequencies of treatable genetic conditions specific to South East Asian populations, which are currently underestimated in existing data sources. This study framework can be adapted to other population groups and expanded to multiple genetic conditions to inform health policies directing precision medicine.
Assuntos
Exoma/genética , Triagem de Portadores Genéticos , Doenças Genéticas Inatas/genética , Predisposição Genética para Doença , Ásia , Etnicidade , Frequência do Gene , Doenças Genéticas Inatas/classificação , Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/patologia , Variação Genética , Genética Populacional , Humanos , Masculino , Metagenômica , Mutação/genética , Medicina de PrecisãoRESUMO
At the time of publication the author Jyn Ling Kuan did not have a master's degree; this has now been amended to BSc. This has now been corrected in the PDF and HTML versions of the article.