Establishing causal relationships from phenotypic, genotypic, and proteomic data. (360G-Wellcome-204979_Z_16_Z)
This project aims, using adrenomedullin and hypertension as an exemplar, to demonstrate the utility of using Mendelian randomisation and experimentally validated local-protein quantitative trait loci (pQTL) in combination. Local-pQTL are pQTL that map to the approximate location of their gene-of-origin. I will determine local-pQTL for the protein adrenomedullin in two isolated cohorts, one from Orkney, Scotland, and the other from Vis, Croatia. I will validate the core assumptions underlying Mendelian randomisation for one of these local-pQTL and determine, in vitro, the effects of polymorphisms at this site on ADM (which encodes adrenomedullin) gene expression and protein concentration. Finally, I will perform Mendelian randomisation in large genotyped datasets. Collectively, this will provide evidence for, or against, a causal effect of adrenomedullin on blood pressure, and represents a paradigm for assessing the causal relationships between other protein intermediates and complex traits.
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Grant Details
| Amount Awarded | 233584 |
| Applicant Surname | Bretherick |
| Approval Committee | Internal Decision Panel |
| Award Date | 2016-09-30T00:00:00+00:00 |
| Financial Year | 2015/16 |
| Grant Programme: Title | PhD Training Fellowship for Clinicians |
| Internal ID | 204979/Z/16/Z |
| Lead Applicant | Dr Andrew Bretherick |
| Partnership Value | 233584 |
| Planned Dates: End Date | 2019-07-31T00:00:00+00:00 |
| Planned Dates: Start Date | 2016-08-01T00:00:00+00:00 |
| Recipient Org: Country | United Kingdom |
| Region | Scotland |
| Sponsor(s) | Prof Brian Walker |