This research aims to investigate the broader implications of mitochondrial DNA variants for a range of diseases and molecular alterations at the level of transcriptomics, epigenomics, and metabolomics. We plan to leverage the vast data resources available from the UK Biobank to analyze the genomic, clinical, and phenotypic data to uncover previously unrecognized links between mitochondrial DNA variant and complex diseases. The project will further inform precision medicine approaches for mitochondrial diseases and provide insights into the molecular mechanisms underlying these conditions.
Mitochondria are central to cellular energy production, and dysfunction in mitochondrial genes is implicated in a wide range of diseases, including metabolic disorders, neurodegenerative diseases, and some mental health conditions. To date, more than 350 mitochondrial DNA variants have been reported globally; however, current research on mitochondrial genetics and its role in human health remains limited, and existing studies have primarily focused on either a single disorder or a specific variant. The exploration of mitochondrial-wide genetic variations and their broader implications for human health is still an under-explored area with immense potential for scientific discovery. A Mitochondria-wide Association Study is a hypothesis-free, high-throughput analytical method used to investigate the relationship between mitochondrial genetic variation and complex human diseases or traits. It is conceptually analogous to a Genome-wide Association Study, but with its scope strictly confined to the mitochondrial genome. It serves as the bridge between basic mitochondrial genetics and clinical epidemiology and allows researchers to survey the entire mitochondrial genome in thousands of individuals simultaneously, providing a statistical framework to quantify how the mitochondrial DNA variants influence human health.