Mitochondrial GWA analysis in several complex diseases using the KORA population

Objectives: Our main goal is to identify mitochondrial susceptibility genes for human complex diseases. Methodology: Using different genotyping platforms and New Generation Sequencing we performed mtGWA analysis in the KORA population (3,080 individuals) with several phenotypes (BMI, cholesterol, post-traumatic stress disorder, thyroid diseases, depression, among others) as well as with life styles (smoking cigarettes, alcohol consumption, and physical activity). Results: we report several mitochondrial genetic variants associated with post-traumatic stress disorders and metabolic syndrome. BMI, HDL cholesterol and TG levels were also associated to mitochondrial variants, indicating that the presence of heteroplasmy in these variants may influence the balance of HDL cholesterol and TG levels. We also observed that no physical activity, alcohol abuse, and smoke cigarettes may increase the heteroplasmy levels of mitochondrial genetic variants. Conclusions: As fluctuations in mtDNA heteroplasmy may signify alterations in cellular activity, our findings highlight the important role of the mtDNA as a biomarker for aging-related diseases and metabolic syndromes.