Complete genomic profiles of 1,496 Taiwanese reveal curated medical insights

Abstract Background Taiwan Biobank (TWB) project has built a nationwide database to facilitate the basic and clinical collaboration within the island and internationally, which is one of the valuable public datasets of the East Asian population. This study provided comprehensive genomic medicine findings from 1,496 WGS data from TWB. Methods We reanalyzed 1,496 Illumina-based whole genome sequences (WGS) of Taiwanese participants with at least 30X depth of coverage by Sentieon DNAscope, a precisionFDA challenge winner method. All single nucleotide variants (SNV) and small insertions/deletions 1 (Indel) have been jointly called and recalibrated as one cohort dataset. Multiple practicing clinicians have reviewed clinically significant variants. Results We found that each Taiwanese has 6,870.7 globally novel variants and classified all genomic positions according to the recalibrated sequence qualities. The variant quality score helps distinguish actual genetic variants among the technical false-positive variants, making the accurate variant minor allele frequency (MAF). All variant annotation information can be browsed at TaiwanGenomes (https://genomes.tw). We detected 54 PharmGKB-reported Cytochrome P450 (CYP) genes haplotype-drug pairs with MAF over 10% in the TWB cohort and 39.8% (439/1103) Taiwanese harbored at least one PharmGKB-reported human leukocyte antigen (HLA) risk allele. We also identified 23 variants located at ACMG secondary finding V3 gene list from 25 participants, indicating 1.67% of the population is harboring at least one medical actionable variant. For carrier status of all known pathogenic variants, we estimated one in 22 couples (4.52%) would be under the risk of having offspring with at least one pathogenic variant, which is in line with Japanese (JPN) and Singaporean (SGN) populations. We also detected 6.88% and 2.02% of carrier rates for alpha thalassemia and spinal muscular atrophy (SMA) for copy number pathogenic variants, respectively. Conclusion As WGS has become affordable for everyone, a person only needs to test once for a lifetime; comprehensive WGS data reanalysis of the genomic profile will have a significant clinical impact. Our study highlights the overall picture of a complete genomic profile with medical information for a population and individuals.