Integration of GWAS identified disease risk variants with epigenomic annotations derived from myeloid cells
Approved Research ID: 66308
Approval date: June 16th 2021
Genome wide association studies (GWAS) have identified genetic variants, i.e. variation in the DNA sequence in each of our genomes, that confer an increased risk to develop a certain trait or disease. These genetic variants are most often not located within genes, but in intergenic regions which are important for regulating gene expression. It is often unclear, however, what specific cell type and what specific genes are affected by these genetic variants.
Previously we showed, that microglia, immune cells of the brain, harbor a majority of genetic risk variants that are linked to an increased risk to develop Alzheimer disease. Here, we propose to provide a catalogue of intergenic regions in monocytes (white blood cells that can differentiate into macrophages) and microglia that are associated with increased risk for various disorders, ranging from neurodegenerative, cardiovascular, metabolic, and autoimmune diseases. To this aim, we will use GWAS data provided by the UC Biobank and overlay these with our comprehensive datasets including gene expression profile of monocytes, monocyte-derived macrophages, and microglia. Findings from this study will open new avenues for deciphering the role of myeloid cells to disease pathogenesis and will open up the avenues for novel intervention targets..