Genetic profiles of 103,106 individuals in the Taiwan Biobank provide insights into the health and history of Han Chinese

Abstract

Personalized medical care focuses on prediction of disease risk and response to medications. To build the risk models, access to both large-scale genomic resources and human genetic studies is required. The Taiwan Biobank (TWB) has generated high-coverage, whole-genome sequencing data from 1492 individuals and genome-wide SNP data from 103,106 individuals of Han Chinese ancestry using custom SNP arrays. Principal components analysis of the genotyping data showed that the full range of Han Chinese genetic variation was found in the cohort. The arrays also include thousands of known functional variants, allowing for simultaneous ascertainment of Mendelian disease-causing mutations and variants that affect drug metabolism. We found that 21.2% of the population are mutation carriers of autosomal recessive diseases, 3.1% have mutations in cancer-predisposing genes, and 87.3% carry variants that affect drug response. We highlight how TWB data provide insight into both population history and disease burden, while showing how widespread genetic testing can be used to improve clinical care.

Fig. 1. Comparison of imputation performance of the TWBv2 array using three reference panels.

The average r² values (a) and concordance (b) are plotted against the minor allele frequency. EAS: reference panel with EAS from 1000 genome; TWB: reference panel with Taiwan biobank NGS data.

Fig. 2. Ancestral diversity of the TWB participants.

Clustering of samples from a Minnan, b Hakka, c East China, d South Central China, e North and Northeast China, and f Southwest China + other East Asian groups.

Fig. 3. Population substructure and population growth estimates.

a Number of novel (non-Taiwanese Minnan) variants for each additional sample stratified by province (axes markings represent latitudes and longitudes). Adapted from the Digital Map Database of China, 2020, “Provincial Boundary”, https://doi.org/10.7910/DVN/DBJ3BX, Harvard Dataverse, V1. b Estimated past population sizes for Taiwanese Minnan.