The clinical utility of genome sequencing is multi-dimensional: experience from the Hong Kong Genome Project

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. 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. 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. 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. 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. Chu, Chung et al. quantify the clinical utility of genome sequencing (GS) using the Clinician-reported Genetic testing Utility InDEx (C-GUIDE) in a diverse cohort from the Hong Kong Genome Project. Findings reveal the highest utility in psychosocial benefits, highlighting that the value of GS is driven more by test results than by patient characteristics.