Mitochondrial (MT) dysfunction is a hallmark of aging and has been associated with most aging-related diseases as well as immunological processes. However, little is known about aging, lifestyle and genetic factors influencing mitochondrial DNA (mtDNA) abundance. In this study, mtDNA 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 the abundance of mtDNA was significantly elevated in women compared to men, was negatively correlated with advanced age, higher smoking exposure, greater body-mass index, higher frailty index as well as elevated red and white blood cell count and 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 mtDNA abundance. By performing a genome-wide association study, we identified 50 independent regions genome-wide significantly associated with mtDNA 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 mtDNA abundance to be around 8%. To investigate the consequence of altered mtDNA abundance, we performed a phenome-wide association study and found that mtDNA abundance is involved in risk for leukaemia, hematologic diseases as well as hypertension. Thus, estimating mtDNA 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.

线粒体 (MT) 功能障碍是衰老的标志，与大多数衰老相关疾病以及免疫过程有关。然而，人们对影响线粒体 DNA (mtDNA) 丰度的衰老、生活方式和遗传因素知之甚少。在这项研究中，从英国生物银行的 295,150 名参与者映射到 MT 基因组的探针的加权强度估计了 mtDNA 丰度。我们发现，与男性相比，女性的 mtDNA 丰度显着升高，与高龄、更高的吸烟暴露、更高的体重指数、更高的虚弱指数以及红细胞和白细胞计数升高和死亡率降低呈负相关。此外，血液中与胆固醇代谢相关的几种生化标志物，发现离子稳态和肾功能与 mtDNA 丰度显着相关。通过进行全基因组关联研究，我们确定了 50 个与 mtDNA 丰度显着相关的全基因组独立区域，这些区域包含多个参与免疫系统、癌症和线粒体功能的基因。使用混合效应模型，我们估计 mtDNA 丰度的 SNP 遗传力约为 8%。为了研究 mtDNA 丰度改变的后果，我们进行了一项全表型关联研究，发现 mtDNA 丰度与白血病、血液病和高血压的风险有关。因此，从基因分型阵列估计 mtDNA 丰度有可能为与年龄和疾病相关的过程提供新的见解，