Disentangling relationships between genotype and phenotype in complex genetic disorders, with particular application to liver and kidney disease

The main goal of this research is to develop and apply advanced statistical methods to help elucidate the biological mechanisms and causal pathways underpinning the correlations seen between genotype and phenotype in complex genetic disorders, with specific emphasis on liver and kidney disease. This will allow us to better understand the biological processes leading to disease development, thus enabling the development of potential therapies and cures. Identifying genes and their protein products which alter disease risk will point to potential new drug targets and allow opportunities for re-purposing of existing drugs. We will use measurements of genetic factors and potential intermediate processes like gene expression, DNA methylation and protein levels, available through long-standing collaborations with clinical colleagues. A key goal of our research is to develop methods that integrate these different data types with one another and with similar data from external sources. We will expand the data available through UK-PBC (SNP-genotypes and gene-expression profiling in 100 pre-treatment cases plus 50 controls), by adding CpG-methylation and serum proteomics, enhancing our ability to identify causal pathways in disease development/progression.This will inform disease biology, subsequent treatment response, and the extent to which it can be predicted from baseline measures.