Exploring the contribution of complex genomic variation to fibrosis risk (360G-Wellcome-337203_Z_25_Z)

The aim of my project is to identify structural variants that are associated with fibrosis risk within and across multiple organs or diseases. In order to achieve this, I will utilise genome-wide association studies (GWAS) and genetic correlation analyses to identify variants that are associated with fibrotic diseases across multiple organ systems, using data from UK Biobank and All of Us. I will use an organ-level approach that is unique to my research group. This means I will be looking at multiple fibrotic diseases within a specific body system at once, instead of looking at each fibrotic disease in turn, to increase sample size (as many fibrotic diseases are rare). This approach has already been utilised within the group for SNP-based GWAS, making the extension to structural variants a worthwhile exploration to investigate missing heritability (in which SNP-based GWAS typically result in lower heritability estimates than twin and family studies). It will also allow for novel mechanistic insights that can inform drug repurposing efforts and provide novel targets. The body systems I aim to investigate are the pulmonary, biliary, integumentary (skin), and liver systems.