Carrier rates for recessive monogenic diseases in the Chinese Han population: a systematic review

In China, research on expanded carrier screening (ECS) has exhibited significant inconsistencies due to regional variations, with a lack of large-scale data analysis of the population nationwide. This study aimed to review the carrier rates of monogenic disorders throughout China comprehensively. The study was conducted in two stages, with the carrier rate of monogenic diseases as the primary outcome. In the first stage, 1449 articles were identified, of which 11 were ultimately included for data extraction. In the second stage, all 307 genes identified by the first stage were specifically investigated, and both carrier rates and allele frequencies of pathogenic or likely pathogenic (P/LP) variants were extracted. Nineteen genes were associated with monogenic disorders exhibiting carrier frequencies above 1/100, including GJB2 (7.78%), HBA1/2 (6.19%), PAH (2.76%), ATP7B (2.51%), DUOX2 (2.50%), HBB (2.48%), GALC (2.37%), CYP21A2 (2.11%), SLC26A4 (1.96%), POLG (1.92%), USH2A (1.91%), SLC25A13 (1.87%), SLC22A5 (1.78%), SMN1 (1.75%), MMACHC (1.66%), G6PD (1.38%), GAA (1.05%), UGT1A1 (1.02%), and TYR (1.01%). Twenty-seven conditions had carrier rates between 1/100 and 1/200, and thirty had carrier frequencies between 1/200 and 1/400. The ten most common pathogenic/likely pathogenic (P/LP) variants with the highest allele frequencies were: GJB2 c.109G>A (7.3%), POLG c.2890C>T (0.94%), GALC c.1901T>C (0.90%), SMN1 exon 7 deletion (0.87%), SLC25A13 c.2T>C (0.59%), SLC22A5 c.1472C>G (0.52%), GJB2 c.235del (0.50%), SLC22A5 c.1400C>G (0.48%), SLC22A5 c.43G>T (0.44%), and SLC25A13 c.852_855del (0.43%). This review provides the first comprehensive summary of carrier rates for monogenic diseases in the Chinese Han population. It not only describes but also ranks the carrier rates and variant frequencies of related genes, offering critical evidence for the tiered inclusion of gene categories in ECS panels or newborn screening programs.