170 Expanded carrier screening: primary prevention of recessive monogenic diseases evaluated using 1,909 chinese genome and exome sequencing data

Background Expanded carrier screening (ECS) is a genetic test that investigates the genetic composition of a couple and determines whether their offspring has an elevated risk of inherited disorders. Comparisons between commercially available ECS has, however, only shown small overlaps in common genes offered for screening. Objectives Compiled with the inadequate information surrounding carrier frequencies in the Chinese population, secondary usage of next generation sequencing could be used in the optimization of ECS panels surrounding clinical utility, public health benefits, and reducing unnecessary socio-psychological stress. Methods In this study, a total of 1543 Southern Chinese and 366 Northern Chinese genome and exome sequencing were screened for carrier status over 315 genes. The gene list curated for this study was compiled from three ECS panels offered by frequently used commercial companies and literature reporting high carrier frequencies for treatable inherited disorder in South East Asia population genomics. Results 180 unique disease-causing variants were identified and 47.8% (n = 738) of Southern Chinese individuals screened in this study harboured at least 1 disease-causing variant. CNV calling determined 4 unique pathogenic or likely pathogenic copy number variants. A total of 285 unique carrier variants were classified as pathogenic or likely pathogenic. Results have also identified 12 genes with a carrier frequency over 1% including GJB2, HBA1/HBA2, SMN1, SLC22A5, SLC25A13, ATP7B, SLC26A4, GALC, POLG, USH2A, and HBB. Conclusions This study shows that secondary analysis of NGS data can illustrate the carrier frequencies in the Southern Chinese population. Through the comparison of different commercially available ECS panels, we identified potential for improvement in the optimization of commercially available ECS panels for the future of precision medicine.