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Next Generation Sequencing (NGS) technology is becoming a powerful tool for the discovery of genetic variants across entire chromosomes. However, it is not yet feasible to apply NGS in a large-scale-population-based genome study due to its relatively high cost and required high computing power. Alternatively, SNP chip genotyping and imputation analysis have been widely used to study hundreds of thousands of samples. Genotype imputation estimates untyped markers of SNP chip using reference panel comprised of thousands of sequenced samples. Reference panels of The 1,000 Genomes Project (1KG) and Haplotype Reference Consortium (HRC) are frequently used as public reference panel. 1KG and HRC include 2,504 multi-ethnic samples and 32,488, mostly European, samples. To date, 622 sequenced samples of Korean Reference Genomes (KRG) have been produced by the Korean National Institute of Health, KCDC. Among these, we have constructed the Korean Reference panel using 397 samples and performed imputation analysis using the reference panel on about 8,000 samples genotyped using Affymetrix 5.0 genotyping chip. We also compared the performance of KRG to those of 1KG. KRG showed comparable performance with 1KG, in terms of average imputation quality and imputation-based genomic coverage. The merged reference panel of KRG and 1KG showed 4-6% increased imputation efficiency compared to the imputation performance using the single reference panel. For genomic study of Koreans, imputation performance will be greatly increased by using the combined reference panels of KRG, 1KG, and other reference panel resources with Asian ancestries.
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