Comprehensive Analysis of Mitochondrial DNA Variation in the Taiwan Biobank: Implications for Complex Traits and Population Genetics

This study presents a comprehensive analysis of mitochondrial DNA (mtDNA) variation in the Taiwan Biobank (TWB), providing insights into the genetic characteristics of the Taiwanese population and the implications of mtDNA in complex traits. We performed mtDNA genotyping on 1,492 individuals using whole-genome sequencing data and imputed mtDNA variants for 101,473 participants from microarray data. Our analysis identified 23 confirmed pathogenic mtDNA variants, with approximately 1 in 180 individuals carrying such variants. Further exploration of mtDNA haplogroups and ancestry revealed no direct correlation between nuclear and mitochondrial genomes, which reflects their distinct inheritance patterns and evolutionary histories. In a mitochondrial genome-wide association study across 86 traits and 306 mtDNA variants, we discovered novel associations between MT-ND2 gene variants and high myopia, as well as 14 mtDNA variants linked to renal function biomarkers. Notably, renal-associated variants clustered into two main groups: ancestral variants of macrohaplogroup M associated with poorer renal function and variants of the B4b sub-haplogroup linked to improved renal function markers. Our findings highlight the importance of population-specific genetic studies, contributing to our understanding of mitochondrial genetics in the Taiwanese population and its implications for health and disease.