Jointly modelling phenotype and function in the fine-mapping and follow-up of disease associated loci. (360G-Wellcome-098759_Z_12_Z)

I will develop a statistical model to be applied to association data across multiple traits (be they end-stage disease phenotypes, intermediate phenotypes, or measures of molecular function). This model will explicitly account for the genetic relationship between traits, and will provide estimates and uncertainty information for important questions, such as which traits are affected by a given variant, and what is the proportion of genetic risk shared between diseases. The first goal of the p roject is to develop and test such methods, and produce working, efficient, open source software for the community to use. The second goal of the project is to apply these methods to a large dataset of genotypes from immune-related diseases, to carefully measure the genetic overlap between these diseases, discover which specific variants contribute to disease risk, and to discover which variants contribute to the unique characteristics of each disease. In the longer term, I will develop colla borations with those who have generated cross-trait data, and help apply my method to their datasets. I will also develop collaborations with experimental biologists to develop high-throughput experimental and statistical techniques to validate hypotheses generated from my research.