Building a platform for genetic inference from the Genomics England data (360G-Wellcome-200186_A_15_Z)

The objective of this proposal is to bring together experts in genome sequence informatics and statistical genetics to generate a set of derived data sets and analysis tools from the 100,000 Genomics England (GEL) genome sequences. The outputs will have high value for studies of human genetics and human disease using both the GEL subjects themselves and third party data. The two main aims are \- Phase the genome sequences to generate the world’s largest haplotype reference panel, empowering very low frequency imputation for future genome wide association studies, via a central imputation server. \- Characterize the fine-scale genetic structure of the English population at an unprecedented level, providing knowledge for population structure matching and adjustment for disease studies. To succeed, we will pool expertize across the aims to build new methods that can handle the unprecedented scale of the dataset, and for the first time combine phasing and population structure analysis in one single step. The proposed research is central to a recently approved, 3-year Genomics England Clinical Interpretation Partnership (GeCIP). The grant will support collaborative activity between researchers, with complementary expertise, at 5 different institutions (Oxford Stats – Marchini, Myers), UCL (Hellenthal), WTSI (Durbin), Bristol (Lawson), WTCHG (McVean).