A genotype imputation reference panel specific for native Southeast Asian populations.

Area of Science:

• Genomics
• Population Genetics
• Bioinformatics

Background:

• Genetic imputation accuracy is crucial for analyzing genome-wide association studies (GWAS).
• Existing reference panels often lack representation of specific ethnic groups, potentially limiting imputation accuracy.
• Southeast Asian populations are underrepresented in global genomic reference datasets.

Purpose of the Study:

• To develop a Southeast Asian-specific (SEA-specific) reference panel.
• To evaluate the imputation performance of the SEA-specific panel against established global panels.
• To assess the impact of ancestry-matched reference panels on imputation quality.

Main Methods:

• Development of a SEA-specific Reference Panel using a Cross-panel Imputation approach.
• Integration of 2550 samples from GA100K, SG10K, and Peninsular Malaysia Orang Asli (OA) datasets.
• Imputation of OA and Singapore Genome Variation Project (SGVP) genotyping datasets using the SEA-specific panel and comparison with 1000 Genomes Project (1KGP), TOPMED, and Human Genome Diversity Project.

Main Results:

• The SEA-specific panel generated more high-confidence variants than 1KGP for both OA and SGVP datasets.
• Superior imputation quality scores (INFO, DR2, R²) were observed for the SEA-specific panel on the OA dataset compared to TOPMED and Human Genome Diversity Project.
• Higher recall and non-reference disconcordance rates indicate the benefit of ancestry-matched reference panels, though panel size may impact accuracy.

Conclusions:

• The developed SEA-specific Reference Panel significantly enhances genetic imputation accuracy for Southeast Asian populations.
• Ancestry-matched reference panels are critical for improving the reliability of genetic imputation.
• Further research may be needed to optimize reference panel size for maximal imputation accuracy.