Background As part of Singapore's effort towards precision medicine tailored to Asian diversity, we describe the implementation of a nationwide reproductive carrier screening program. Using a customised 112-gene panel, incorporating population-specific recessive genetic diseases, we outline the overall program design, and initial efforts of community and stakeholder engagement, to inform culturally appropriate implementation. Methods Participants receive culturally tailored online education regarding our reproductive screening program and are provided results with genetic counselling and reproductive options. Community and stakeholder perspectives were assessed through questionnaires and consultations with religious leaders. Results Recruitment is nation-wide, and since initiation of our pilot phase in September 2024, 1,619 couples have registered interest, with 60% uptake of those deemed eligible. Among the 456 couples that have received results to date, four couples (0.9%) were identified to be at increased risk. Community questionnaire responses (n=1002), involving couples who participated in the program as well as the general public, indicated interest is high (59%) across the cohort but awareness, intent to participate and implications for reproductive options differed by sociodemographic factors such as ancestry and religion. Healthcare professional respondents (n=113) acknowledged carrier screening will be routine in medical care, but report limited confidence and resources. Engagement with religious leaders indicated support for the program. Conclusion These early program outcomes and community engagement are guiding the implementation of expanding population-based carrier screening in Singapore, contingent on addressing practical challenges through equitable outreach and professional training.

SSJ is co-founder of Global Gene Corp Pte Ltd and Rhea Health Pte Ltd. SSJ has received travel allowances from Illumina, Pacific BioSciences and Oxford Nanopore. DA is Medical Director at Eugene Labs. WK is co-founder of Rhea Health Pte Ltd. GB and JC are on the scientific advisory board of Rhea Health Pte Ltd. The rest of the authors declare that they have no competing interests.

This study is funded by the carrier screening grant MCHRI/FY2023/EX/152-A207, AM/ACP-Designated Philanthropic Fund Award MCHRI/FY2023/EX/152-A207 through Temasek Foundation and AM Strategic Fund Award PRISM/FY2022/AMS(SL)/75-A137, SUNRISE SingHealth Duke-NUS AM Strategic Fund Award PRISM/FY2022/AMS(SL)/75-A137, National Precision Medicine (NPM) Phase II is supported by the National Research Foundation, Singapore (NRF) under the RIE2020 White Space (MOH-000588 and MOH-001264) funding initiative. NPM Phase III is supported by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd under the NMRC RIE2025 NPM Phase III Funding Initiative (MOH-001734). The community questionnaire study is supported by the Social Science Research Council (Singapore) and administered by the Ministry of Education, Singapore, under its Social Sciences Research Thematic Grant (SSRC2023-SSRTG-006). This research was also supported by the Commonwealth through an Australian Government Research Training Program Scholarship [DOI: https://doi.org/10.82133/C42F-K220]. SSJ is supported by National Medical Research Council Clinician Scientist Award (NMRC/CSAINVJun21-0003) and (NMRC/CSAINV24jul-0001). WKL is supported by National Precision Medicine Programme (NPM) PHASE II FUNDING (MOH-000588).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics approval and consent from participants consenting to take part in the carrier screening program and questionnaires was obtain from SingHealth Centralised Institutional Review Board (2019/2243). All experiments were performed in accordance with relevant guidelines and regulations. This research conforms to the principles of the Helsinki Declaration.

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The datasets analysed during the current study are available in the supplementary files and further information is available from the corresponding author on reasonable request.