Customizing carrier screening in the Chinese population: Insights from a 334-gene panel

This study aimed to evaluate the yield and applicability of expanded carrier screening and propose carrier rate screening thresholds suitable for the Chinese population by comparing the current screening panel with the American College of Medical Genetics and Genomics recommended panel of 113 genes.

Using targeted next-generation sequencing, a customized panel with 334 genes was performed on 2168 individuals without clinical phenotypes for expanded carrier screening purpose. Variant interpretation followed the American College of Medical Genetics and Genomics guidelines. Carrier rates were calculated for each identified variant and each gene. At-risk couple rates were also assessed. The yield of expanded carrier screening was evaluated through calculating cumulative carrier rate.

Overall, 65.87% of the individuals were found to be carriers of at least 1 disease causing variants. The overall at-risk couple rate was 11.76%, of which the GJB2:c.109G > A related at-risk couple rate was 5.78%. The cumulative carrier rate of 334-panel was 65.53%. When screened genes with gene carrier rate ≥1/1000, the expanded carrier screening can cover over 90% of the cumulative carrier rate and at-risk couples. A total of 86 genes overlapped with American College of Medical Genetics and Genomics Tier-3 genes and were attributed to the cumulative carrier rate of 47.33%.

Expanded carrier screening using the 334-gene panel showed high screening efficiency. A threshold of gene carrier rate ≥1/1000 is recommended for selecting carrier screening genes in the Chinese Han population. This study highlights the importance of customizing screening panels based on the ACMG Tier-3 genes in conjunction with population-specific carrier frequencies to improve the accuracy and effectiveness of expanded carrier screening.