The causal map of the human phenome (360G-Wellcome-208806_Z_17_Z)
This fellowship is focused on maximally exploiting GWAS summary data and 2SMR methodology. I will: 1. Create a computational framework that can construct and represent the causal map of the measured human phenome. Using existing (MR-Base) and upcoming (e.g. GoDMC, UK Biobank) data sources I will construct a graph of pairwise causal relationships between thousands of traits. Each causal relationship will be assessed using all available 2SMR and sensitivity methods to ensure transparency and highest standards for hypothesis-driven causal inference. 2. Exploit the graph to improve a) reliability of causal estimates by empirically assessing pleiotrpy; b) statistical power by exploiting outliers in the data to search for putative novel associations, and using graph traversal algorithms to find links for which direct associations are underpowered; c) interpretability by deconvolving the mediating relationships between arbitrary numbers of traits. 3. Use the causal graph as a tool for phenomic modelling. Example 1: linking molecular phenotypes to new or existing drug targets will enable the prediction of the efficacy and safety of developing interventions. Example 2: using MR against fitness related traits to obtain selection coefficients for each phenotype, I will construct models of human evolution, investigating the cost of complexity and evolutionary trajectories.
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Grant Details
Amount Awarded | 809240 |
Applicant Surname | Hemani |
Approval Committee | Sir Henry Dale Fellowship Interview Committee |
Award Date | 2017-10-18T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Sir Henry Dale Fellowship |
Internal ID | 208806/Z/17/Z |
Lead Applicant | Dr Gibran Hemani |
Partnership Name | Royal Society/Wellcome Trust Sir Henry Dale Fellowship |
Partnership Value | 809240 |
Planned Dates: End Date | 2023-09-27T00:00:00+00:00 |
Planned Dates: Start Date | 2018-04-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South West |
Sponsor(s) | Prof George Davey Smith |