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Objectives: To evaluate the clinical utility of expanded carrier screening (ECS) in Chinese preconception and prenatal populations, focusing on carrier frequency and the impact on at-risk couples (ARCs)., Methods: Data from 6,298 Chinese individuals from 4,420 families who underwent a 149-gene ECS panel at a single center were analyzed. The prevalence of positive carriers and ARCs was determined, with follow-up on reproductive decisions and pregnancy outcomes for ARCs., Results: Of the individuals screened, 2,673 (42.4 %) were carriers of at least one pathogenic or likely pathogenic variant, and 98 (2.22 %) ARCs were identified. GJB2-related deafness and Duchenne muscular dystrophy were the most common autosomal recessive (AR) and X-linked disorders. Screening the top 11 (gene carrier rate [GCR] ≥ 1/100), 22 (GCR ≥ 1/200), and 41 (GCR ≥ 1/331) AR genes could identify 53.5 %, 67.9 %, and 81.3 % of variants, respectively. The corresponding ratios for identified ARCs were 90.4 %, 94.0 %, and 100 %. Follow-up data from 80 ARCs indicated that 75.0 % (60/80) took significant action based on the ECS results. Additionally, four families (3.5 %, 4/115) were identified at risk for a second disease unrelated to their initial family monogenic history., Conclusions: This study, representing the largest cohort of a moderate-sized ECS panel test in the Chinese population, demonstrates the clinical utility of ECS in both healthy individuals and those with a family history of monogenic disorders. The data obtained provide valuable insights for developing a Chinese-specific ECS panel. Tailored approaches are critical for wider adoption and successful routine application of ECS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The number and distribution of recessive alleles in the population for various diseases are not known at genome-wide-scale. Based on 6,447 exome sequences of healthy, genetically unrelated Europeans of two distinct ancestries, we estimate that every individual is a carrier of at least 2 pathogenic variants in currently known autosomal-recessive (AR) genes and that 0.8%-1% of European couples are at risk of having a child affected with a severe AR genetic disorder. This risk is 16.5-fold higher for first cousins but is significantly more increased for skeletal disorders and intellectual disabilities due to their distinct genetic architecture., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)