Somatically acquired whole chromosome loss in nucleated blood cells is an indicator of immune aging and genomic instability. However, little is known about aging, lifestyle and genetic factors influencing mitochondrial (MT) DNA abundance. In this study, MT DNA abundance was estimated from the weighted intensities of probes mapping to the MT genome in 295,150 participants from the UK Biobank. We found that abundance of MT DNA was significantly elevated in women compared to men, was negatively correlated with advanced age, more packyears, greater body-mass index, higher frailty index as well as elevated red and white blood cell count and, importantly, lower mortality. In addition, several biochemistry markers in blood related to cholesterol metabolism, ion homeostasis and kidney function were found to be significantly associated with MT DNA abundance. By performing a genome-wide association study, we identified 50 independent regions genome-wide significantly associated with MT DNA abundance which harbour multiple genes involved in the immune system, cancer as well as mitochondrial function. Using mixed effects models, we estimated the SNP-heritability of MT DNA abundance to be around 8%. To investigate the consequence of altered MT DNA abundance, we performed a phenome-wide association study and found that MT DNA abundance is involved in risk for leukaemia, hematologic diseases as well as hypertension. Thus, estimating MT DNA abundance from genotyping arrays has the potential to provide novel insights into age- and disease relevant processes, particularly those related to immunity and established mitochondrial functions. ### Competing Interest Statement The authors have declared no competing interest.

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