SUGAR – Identification of disease-causing molecular targets in obesity-related traits and diabetes by integrating multi-omics layers (Prof. Dr. Markus Scholz, abgeschlossen)
Our ultimate goal is to identify causal molecular processes that link obesity-related traits with type 2 diabetes as major sequela of obesity. Furthermore, we aim to provide targets to modify these processes. For this purpose, we perform an integrative multi-omics approach in three independent cohorts (Sorbs, LIFE-Adult, LIFE-Heart) for which comparable genetic, transcriptomic, and metabolomic data are available.
We aim to establish causal links between these molecular layers and obesity-related traits, namely classical anthropometric measures, MRI-based fat distribution, and 3D anthropometry. Additionally, we will analyze reverse causalities, i.e. molecular features that are affected by obesity related traits, and whether these features provide a causal link towards diabetic risk. This will also improve the understanding of molecular mechanisms behind the phenomenon of healthy obese and diseased lean subjects. Causal inference is performed using modified Mendelian randomization approaches and mediation analyses. The most promising genes will be functionally validated as potential therapeutic targets by expression and methylation quantitative trait analyses of visceral and subcutaneous tissue and by studying siRNA knock-down and gene-editing effects on adipocyte development and function.
Laufzeit: 01.11.2017 – 30.04.2020
Institut für Medizinische Informatik, Statistik und Epidemiologie
04107 Leipzig, Germany