Project Details
Projekt Print View

Mitochondrial genome wide association studies with metabolomics and lifestyle factors

Subject Area Epidemiology and Medical Biometry/Statistics
Human Genetics
Term from 2018 to 2021
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 392594259
 
In the era of personalized medicine with more and more patient specific targeted therapies being used, we need reliable, dynamic, faster, and yet sensitive biomarkers both to track the causes of disease and to develop and evolve therapies during the course of treatment. Understanding the mechanisms that control human health and disease, in particular the role of genetic predispositions and their interaction with environmental factors, is a prerequisite for the development of safe and efficient therapies for complex disorders.The emerging field of metabolomics, a high-throughput global metabolite analysis technique, is a burgeoning field, which in recent times has shown substantial evidence to support its emerging role in diagnosis and prognosis of cardiometabolic diseases, as well as its impact in identifying novel cancer biomarkers and developing cancer therapeutics. Recently, genome-wide association studies for the mitochondrial genome have revealed some new genetic factors underlying several complex diseases. Altered mitochondrial electron transport systems and respiratory chain disorders have been known to induce significant changes in metabolic pathways in cancer and other complex diseases. Additionally, research suggests that the progressive accumulation of mutations in the mitochondria over the lifetime of a person may play an important role in age-related diseases and in the normal process of aging.The purpose of the current project is to investigate how the mitochondrial genome may underly the development of human complex diseases in two ways:AIM 1Using sequencing data of the mitochondria from the KORA F4 population (3,080 individuals) we will conduct association analyses between metabolomics and variants of the whole mitochondrial genome to identify genetic variants influencing metabolite profiles. AIM 2Using sequencing data of the mitochondria from the KORA FF4 population (2,279 individuals) and sequencing data of the mitochondria from the KORA F4 population (the same 2,279 individuals but 7 years earlier), we will investigate how mutations that accumulate over time in the mitochondrial genome may be associated to lifestyle factors.Mitochondrial genetic variants that associate with changes in the homeostasis of key lipids, carbohydrates or amino acids are expected to display larger effect sizes than nuclear genetic variants due to their direct involvement in metabolite conversion modification. Recent advances in metabolomics and next-generation sequencing open the window of opportunity to analyze and understand the metabolic pathways controlled by mitochondrial genes and their variants. Thereby, the analysis of mitochondrial genetic variants may provide access to the underlying molecular disease-causing mechanisms.
DFG Programme Research Grants
 
 

Additional Information

Textvergrößerung und Kontrastanpassung