Mitochondrial variation in Taiwan Biobank reveals ancestry structure and trait associations

Mitochondrial DNA (mtDNA) variation contributes to human health, but its role in the Taiwanese population remains largely unexplored. Here, we comprehensively analyzed mtDNA variation in the Taiwan Biobank (TWB) by genotyping 1,492 individuals using whole-genome sequencing and imputing variants for 101,473 participants from microarray data. We identified 23 pathogenic mtDNA variants, with approximately 1 in 180 individuals carrying such variants. Analyses of mitochondrial genetic diversity revealed subtle differentiation among maternal ancestry groups. A mitochondrial genome-wide association study across 86 traits identified novel links between MT-ND2 variants and high myopia, as well as 14 variants associated with renal function biomarkers. Notably, renal-associated variants clustered into two groups: ancestral variants of macrohaplogroup M associated with reduced renal function and B4b sub-haplogroup variants linked to improved function. These findings highlight the value of population-specific mtDNA studies in advancing our understanding of mitochondrial genetics and health.