Unravelling the genetic control over immune-cell levels.

The immune system is a complex interactive system of different types of leukocytes, whose primary purpose is to defend the body against infectious diseases and pathogens. However, imbalances in leukocyte levels can drive autoimmunity and allergy, and thus the levels of each cell type are critical. To date, systematic assessment of the role of genetic variation on the immune system has been limited. Recently developed technologies enable the analysis of large populations by genome-wide association (GWA) studies. This prompted the first GWA study of immune cell types in healthy individuals from Sardinia (a population considered as a distinct genetic isolate), demonstrating the feasibility of finding associations between genetic variants and multiple immune cell variation. In this project we will perform the first GWA study on a unique extended set of immune phenotypes covering the adaptive immune system (T and B cells) in a non-isolated European population of 577 healthy individuals, collected at the University Hospitals Leuven. We will use the GWA approach, novel genetic analysis methods and functional experiments to i) detect and characterize novel genetic loci for immune cell types, ii) dissect the genetic mechanism that underlies genetic associations with multiple immunophenotypes and iii) explore the processes contributing to the development of autoimmune disease. Findings from this project will provide insights into the underlying biology of immune-mediated diseases.