A genetic approach to characterising the role of the serum metabolome in type 2 diabetes (360G-Wellcome-105373_Z_14_Z)
Background: Large-scale profiling of the human metabolome could provide new insight into pathways related to the development of T2D. Mendelian randomization is an approach that uses genetic "instruments" to assess causality of observational associations, but this has not yet been adopted for systematic investigation of causality of T2D-related differences in the serum metabolome. Aims: 1\. To prioritize metabolites associated with T2D for causality assessment. 2\. To develop genetic "instruments" for the serum levels of high-priority metabolites. 3\. To use these instruments to assess the causal nature and sequence of associations between metabolite levels and T2D. Methods: 1\. High-priority metabolites will be identified through a systematic literature review of prospective studies investigating T2D-related differences in the serum metabolome, and a novel discovery in the EPIC-Norfolk T2D case-cohort study. 2\. Genome-wide data from the EPIC-Norfolk and Fenland studies will be meta-analysed with publicly available data to identify genetic variants associated with each metabolite and derive and validate genetic instruments. 3\. Unconfounded causal effect sizes of metabolite to T2D associations will be estimated using instruments developed in stage 2 by meta- analysing results from publicly available T2D GWAS results with new data from the InterAct T2D case-cohort study and UK Biobank.
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Grant Details
| Region | East of England |
| Award Date | 2014-02-10T00:00:00+00:00 |
| Sponsor(s) | Prof Sir Stephen O'Rahilly |
| Internal ID | 105373/Z/14/Z |
| Planned Dates: End Date | 2018-09-30T00:00:00+00:00 |
| Planned Dates: Start Date | 2014-10-01T00:00:00+00:00 |
| Amount Awarded | 160792 |
| Financial Year | 2013/14 |
| Lead Applicant | Mrs Mrs L Wittemans Wittemans |
| Grant Programme: Title | PhD Studentship (Basic) |
| Applicant Surname | Wittemans |
| Approval Committee | PhD Studentships |
| Recipient Org: Country | United Kingdom |
| Recipient Org: City | Cambridge |
| Has the grant transferred? | No |
| Research conducted at multiple locations? | No |
| Total amount including partnership funding | 160792 |