KoVariome: Korean National Standard Reference Variome database of whole genomes with comprehensive SNV, indel, CNV, and SV analyses

High-coverage whole-genome sequencing data of a single ethnicity can provide a useful catalogue of population-specific genetic variations, and provides a critical resource that can be used to more accurately identify pathogenic genetic variants. We report a comprehensive analysis of the Korean population, and present the Korean National Standard Reference Variome (KoVariome). As a part of the Korean Personal Genome Project (KPGP), we constructed the KoVariome database using 5.5 terabases of whole genome sequence data from 50 healthy Korean individuals in order to characterize the benign ethnicity-relevant genetic variation present in the Korean population. In total, KoVariome includes 12.7M single-nucleotide variants (SNVs), 1.7M short insertions and deletions (indels), 4K structural variations (SVs), and 3.6K copy number variations (CNVs). Among them, 2.4M (19%) SNVs and 0.4M (24%) indels were identified as novel. We also discovered selective enrichment of 3.8M SNVs and 0.5M indels in Korean individuals, which were used to filter out 1,271 coding-SNVs not originally removed from the 1,000 Genomes Project when prioritizing disease-causing variants. KoVariome health records were used to identify novel disease-causing variants in the Korean population, demonstrating the value of high-quality ethnic variation databases for the accurate interpretation of individual genomes and the precise characterization of genetic variations.The authors thank many people not listed as authors who provided analyses, data, feedback, samples, and encouragement. Especially, thanks for Sunghoon Lee, Taehyung Kim, Sanghoon Song, Sangsoo Kim, and George Church. This work was supported by the 2014 Research Fund (1.140113.01 and 1.150014.01) and the 2016 Research Fund (1.160052.01) of Ulsan National Institute of Science & Technology (UNIST) and supported by the Ministry of Trade, Industry & Energy (MOTIE, Korea) under Industrial Technology Innovation Programs 'National Center for standard Reference Data', No. 10075262. This work was also supported by the Research Fund (14-BR-SS-03) of Civil-Military Technology Cooperation Program and the Next-Generation Information Computing Development Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2016M3C4A7952635). This research was also supported by the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (MSIT) (NRF-2017M3C9A6047623). This work was supported by the Genome Korea Project in Ulsan (200 genome sequencing) Research Fund (1.180024.01) of UNIST