Multi-omics analysis to delineate drugresponse pathways
Host: UNIVERSITAIR MEDISCH CENTRUM GRONINGEN (The Netherlands)
PhD awarding institution: UNIVERSITAIR MEDISCH CENTRUM GRONINGEN (The Netherlands)
Lead Supervisor: C Wijmenga
Objectives: Response to drugs is highly heterogeneous. On average medication works in only 25% of cases, and efficacy varies between patients. ESR 12 will develop stratification rules for individuals, based on genetics. For this to be effective, deep understanding of the role of drug-metabolizing SNPs in drug response pathways, and interactions with pertinent biological mechanisms and disease pathways is necessary. 1) To expand on this by investigating the molecular pathways in predicted responders and non-responders using multi-omics data (genomics, RNA-seq, methylation, metabolomics, microbiome). 2) To exploit a population-based cohort (cross-sectional) of ~1500 individuals (LifeLines-Deep – Tigchelaar et al. 2015) for which the multi-omics data have been generated already and from which 1000s of phenotypes are known, using PheWas analysis. 3) Stratify individuals based on existing knowledge about the impact of genetic variation on drug response and investigate the downstream biological consequences in a wealth of molecular parameters. At the same time, the drug metabolizing SNPs will be assessed for any impact on other clinical phenotypes.