Abstract
Background
Assessing clinical utility of genome sequencing (GS) is essential for healthcare decisions. This study quantified the multidimensional utility of GS using the validated Clinician-reported Genetic testing Utility InDEx (C-GUIDE) within a diverse rare disease cohort at the Hong Kong Genome Project.
Methods
Adult and paediatric patients suspected of genetic disorders were recruited from the Hong Kong Children’s Hospital. Clinical geneticists evaluated GS utility based on 17 items. Total C-GUIDE utility scores and global item scores were calculated, with individual item scores ranging from −2 to 2.
Results
Between March and July 2024, three clinical geneticists completed 247 C-GUIDE ratings for 245 probands, with 25% receiving positive, 7% inconclusive, and 69% negative GS results. Total C-GUIDE scores ranges from −1 to 30, with a mean of 6.1 (SD = 10.0). Multivariate regression analysis indicates that positive GS findings are associated with a 16.9-point increase in C-GUIDE scores compared to inconclusive or negative results (p < 0.001). Notably, the highest mean scores are observed in psychosocial benefits for patients and families, regardless of GS results. The mean global item score, representing overall assessment of clinical utility, is 0.53 (SD = 0.06). Baseline patient characteristics are not independently associated with C-GUIDE scores.
Conclusions:
This study represents the first and largest of its kind in the Asia Pacific region, highlighting the multidimensional benefits of GS and the importance of nationwide Genome Projects. By highlighting that clinical utility is primarily influenced by test results rather than patient characteristics, this study underscores the importance of equitable GS implementation across populations.
Plain language summary
Genome sequencing (GS) is a next-generation sequencing technology that reads a person’s complete DNA, enabling the comprehensive detection of genetic variants related to diseases. Its value is often viewed in terms of its diagnostic benefits for patients, mainly through changes in their medical care. This study examined the broader impact of GS on patients involved in the Hong Kong Genome Project, the first large-scale GS project in Hong Kong which aims to enhance the clinical application of GS to benefits patients and their families. It reveals that the most significant benefits are related to emotional and social well-being, also known as psychosocial well-being, regardless of whether the GS results were positive, inconclusive, or negative. We found that the perceived value of GS is influenced more by the test results rather than by patients’ characteristics like age or gender. This highlights the potential for equitable access to GS for all individuals across diverse populations. By recognising these multi-dimensional benefits, we can enhance the implementation of GS in healthcare, ultimately improving patient support and well-being.
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Data availability
Variants identified in the diagnostic cohort were uploaded to ClinVar in batches. (https://www.ncbi.nlm.nih.gov/clinvar/submiTers/510250/). Deidentified individual-level genotype of variants associated with the diagnostic cohort presented in this manuscript and additional aggregate-level data not included in the manuscript is currently available to researchers upon reasonable request by following these steps: 1. Researchers should submit a Data Access Request to HKGI (hkgi_gc_team@genomics.org.hk) outlining the proposed research, including its purpose, scope of data to be accessed and researcher information. 2. The HKGI Data Access Review Panel will review the application in a quarterly meeting to assess the scientific, clinical, technical, resource and regulatory feasibility of the proposal. All feasible proposals will be approved. 3. The HKGI team will collaborate with applicants to prepare the formal proposal and related Institutional Review Board (IRB) documentation. 4. Anonymous, aggregate data will then be provided to applicants either directly or within designated HKGI facilities (for 3–12 months), depending on the assessment of the proposal. The same application process also applies to other individual-level genomic data beyond this manuscript. As the HKGP is actively recruiting new participants at the time of writing, access to such data will be granted to external researchers after the completion of the main phase of this project in 2030. The datasets related to C-GUIDE scoring generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We would like to thank all members of the Hong Kong Genome Institute in preparing the launch of the Hong Kong Genome Project. This work would not have been possible without the instrumental leadership and guidance from Dr. Su-vui Lo, Chief Executive Officer of the Hong Kong Genome Institute. We wish to acknowledge members of the HKGI Scientific Team and Child Health Evaluative Sciences of the Hospital for Sick Children for rounds of translation and contextualisation of the C-GUIDE tool for the HKGP. We thank all patients and family members for participating in the HKGP. We extend our appreciation to the healthcare and recruitment teams at the Partnering Centres of HKGI for their efforts in recruiting and managing the patients and families. The authors would like to express their gratitude to the Board of Directors and Advisory Committees for their continuous support and advice, as well as to the key HKGP stakeholders—the Health Bureau, Hospital Authority and Department of Health—for their overall coordination and financial support of the project. The HKGP is a publicly funded genome sequencing initative commissioned by the Health Bureau of the HKSAR Government. The sponsor had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.
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A.T.W.C., C.C.Y.C. and B.H.Y.C. contributed to the conception and design of the study. A.T.W.C., C.C.Y.C., R.H., S.L. and B.H.Y.C. led the translation and contextualisation of the C-GUIDE tool for the HKGP. C.C.Y.C., H.M.L., S.S.W.C. and B.H.Y.C. carried out acquisition, analysis, or interpretation of data. C.C.Y.C. conducted the statistical analyses and was involved in data organisation and presentation. C.C.Y.C. drafted the manuscript. A.T.W.C., H.M.L., S.S.W.C., R.H., S.L. and B.H.Y.C. critically reviewed the manuscript with suggestions for improvement and revision. A.T.W.C. and B.H.Y.C. oversaw and supervised the project. All authors contributed to the overall data interpretation, reviewed and approved the final draft for submission.
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Communications Medicine thanks Zornitza Stark, Matheus Wilke and the other anonymous reviewer for their contribution to the peer review of this work.
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Chu, A.T.W., Chung, C.C.Y., Luk, H.M. et al. The clinical utility of genome sequencing is multi-dimensional: experience from the Hong Kong Genome Project. Commun Med (2026). https://doi.org/10.1038/s43856-026-01441-9
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DOI: https://doi.org/10.1038/s43856-026-01441-9
