Large prospective biobank studies with genetic data and linkage to health records can play an important role in drug development. Most drugs target specific proteins and functional genetic variants can modify the expression and/or activity of proteins which may be potential drug targets. These naturally occurring variations in human populations can help us to prioritise targets based on predicted efficacy, assessment of safety, identification of potential alternative indications, and to design clinical studies (e.g. choose appropriate outcome measures). Building on our previous work on several East Asian-specific genetic variants (e.g. Lp-PLA2, CETP) that mimic known drug effects, we will continue to undertake and develop phenome-wide association study (PheWAS) approaches to validate known drug targets, and to explore novel targets for different diseases and traits (e.g. blood pressure, obesity) based on the large number of functional variants captured in the CKB genotyping array. We will also use the emerging multi-omics datasets to explore novel biological pathways associated with genetic variants representing potential therapeutic targets.
Our key objectives are:
- to develop and enhance pipelines for phenome-wide analysis of functional genetic variants, using physical measurements, bioassays and electronic health records (e.g. phecodes)
- to identify alternative indications for established drugs (‘repurposing’) by assessing associations of relevant genetic variants with a range of diseases
- to assess the efficacy and safety of drug targets at different stages of clinical development, through disease-specific and phenome-wide analyses of functional genetic variants
- to screen for potential novel targets for specific disease areas such as cardiovascular, cancer metabolic, and neurological diseases, through genome-wide and targeted approaches
- to identify the phenotypic and clinical impacts of variations in biological pathways and systems, through use of multi-omics datasets and biological databases.
Analyses in CKB will be complemented with research in other populations (e.g. UK Biobank), and use of publicly available datasets. Certain projects will be developed in collaboration with industry partners.