A genotype imputation reference panel specific for native Southeast Asian populations

Abstract

We report the development of a “Southeast Asian Specific (SEA-specific) Reference Panel” through a “Cross-panel Imputation” approach, consisting of 2550 samples derived from the GA100K, SG10K, and the Peninsular Malaysia Orang Asli (OA) datasets, covering 113,851,450 variants. The SEA-specific panel produced more high confidence variants than 1000 Genomes Project (1KGP) when imputing the OA (8.9 million SEA-specific vs 8.1 million 1KGP) and the Singapore Genome Variation Project (SGVP) (12.5 million SEA-specific vs 11.8 million 1KGP) genotyping datasets. Further, the SEA-specific panel imputed SNPs with better estimated quality scores (INFO, DR2 and R 2 ) on the OA genotyping dataset when comparing with TOPMED and the Human Genome Diversity Project, but performed similarly on SGVP dataset. This panel also exhibited higher recall and non-reference disconcordance rates, indicating the influence of ancestry closeness of the reference panel. However, we note that the imputation accuracy may be compromised by the size of the reference panel.