Population-scale genomic medicine with the Hong Kong Genome Project

Area of Science:

• Genomics
• Precision Medicine
• Population Health

Background:

• The Hong Kong Genome Project (HKGP) aims to establish a genomic resource for precision medicine in the Chinese population.
• Large-scale genome sequencing and integrated analyses are crucial for understanding genetic variation.

Purpose of the Study:

• To report findings from over 20,000 HKGP participants across rare disease and population cohorts.
• To assess the diagnostic yield of genomic sequencing in rare diseases and identify medically actionable findings in the general population.
• To evaluate the utility of existing genomic panels for the Chinese population and identify population-specific genetic insights.

Main Methods:

• Whole-genome sequencing and integrated analyses were performed on two cohorts: 2,227 rare disease patients and 18,261 population participants.
• Diagnostic rates were calculated for the rare disease cohort.
• Population cohort data were analyzed for pathogenic variants in dominant and recessive disorders, comparing findings against European-ancestry-based panels.
• Pharmacogenomic analysis was conducted to identify actionable phenotypes.

Main Results:

• The rare disease cohort achieved a 25% diagnostic rate.
• In the population cohort, 3.7% had pathogenic variants for dominant disorders when benchmarked against European panels.
• Analysis revealed 38 additional clinically important genes missed by European-based panels for recessive disorders in the Chinese population.
• Nearly all participants had actionable pharmacogenomic phenotypes, potentially impacting millions of prescriptions annually.

Conclusions:

• The HKGP provides a curated reference for Hong Kong Chinese genetic variation, crucial for precision medicine.
• Genomic screening reveals significant diagnostic potential in rare diseases and actionable pharmacogenomic insights.
• The project highlights the need for population-specific genomic resources and challenges the universal applicability of ancestry-based genetic panels.
• HKGP serves as a blueprint for implementing precision medicine in underrepresented populations.