Expanding carrier screening: beyond the genes, to include underrepresented ancestries

Expanding carrier screening: beyond the genes, to include underrepresented ancestries

npj Genomic Medicine

10.1038/s41525-025-00545-w

https://doi.org/10.1038/s41525-025-00545-w

Yasmin Bylstra, Pua Chee Jian, Sui Lin, Jeannette Goh, Christina Choi, Jing Xian Teo, Sandy Lim, Jan Hodgson, Melody Menezes, Ruifen Weng, David J. Amor, Weng Khong Lim, Saumya S. Jamuar

26 December 2025

Bylstra, Y., Jian, P. C., Lin, S., Goh, J., Choi, C., Teo, J. X., Lim, S., Hodgson, J., Menezes, M., Weng, R., Amor, D. J., Lim, W. K., & Jamuar, S. S. (2025). Expanding carrier screening: beyond the genes, to include underrepresented ancestries. Npj Genomic Medicine, 11(1). https://doi.org/10.1038/s41525-025-00545-w

Reproductive carrier screening has evolved beyond ethnic-specific testing to include diverse populations, yet gene selection varies considerably. In Singapore, genomic data analysis identified severe paediatric conditions amongst Chinese, Indian and Malay populations absent from existing screening panels. We developed a model leveraging data from 9051 participants to guide gene selection for carrier screening representative of Asian genetic diversity, focusing on severe paediatric-onset conditions prevalent in these populations. After evaluating severity, genotype-phenotype variability, clinical utility and technical feasibility, we identified 88 genes associated with recessive severe paediatric onset prevalent amongst Chinese, Indian and Malay populations, irrespective of carrier frequency. Including 24 additional genes from our registry resulted in a 105-gene panel, predicted to identify 0.44% at-risk couples, with 86 genes overlapping existing panels. Broadening criteria to include moderate severity conditions while limiting carrier frequencies to less than 1 in 200 reduced the panel to 59 genes, increasing predicted at-risk couples to 0.47%, due to higher carrier frequencies, yet introducing counselling complexities from greater clinical variability. Using local genomic data, we identified genetic conditions relevant to Asian populations for carrier screening. Expanding national genomic sequencing initiatives provides an opportunity to assess genetic condition prevalence across diverse ancestries, improving equity in carrier screening programmes.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This research / project is supported by the Temasek Foundation - AM/ACP-Designated Philanthropic Fund Award
Grant Reference no. : MCHRI/FY2023/EX/152-A207

This research / project is supported by the National Medical Research Council - AM Strategic Fund Award
Grant Reference no. : PRISM/FY2022/AMS(SL)/75-A137.

This research / project is supported by the National Medical Research Council - Clinician Scientist Award
Grant Reference no. : NMRC/CSAINVJun21-0003 and NMRC/CSAINV24jul-0001

This research / project is supported by the Ministry of Health - National Precision Medicine Programme PHASE II FUNDING
Grant Reference no. : MOH-000588

This research / project is supported by the National Research Foundation - Innovation & Enterprise (I&E) Translation Funding initiative
Grant Reference no. :

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https://doi.org/10.1038/s41525-025-00545-w