Statistical methods for studying multidimensional mediators of genetic associations with chronic diseases. (360G-Wellcome-107617_Z_15_Z)

This project aims to develop methods to study mediation via high-dimensional OMICs biomarkers of genedisease associations, ie to identify which biomarkers lie on important pathways from genes to disease, with the ultimate aim of identifying therapeutic targets for new drugs, as well as new indications for existing drugs. The main challenge is coping with the high-dimensionality of the biomarkers. I will investigate novel and existing dimension-reduction methods on the mediators, and then use th e reduced set of mediators in a multiple mediators analysis, with appropriate allowances for the first step. Motivated by studies in which subjects are followed up for CVD (or other chronic disease) events, this will require extending methods for multiple mediation analysis to deal with time-to-event outcomes and time-updated biomarker data. As well as deriving the theoretical properties of the resulting estimators, I will investigate their performance (including robustness to modelling assumpt ions, measurement error, bimodal and truncated distribution of biomarkers) in simulation studies, and apply the most promising approaches to the analysis of several rich datasets, such as the UCLEB consortium of 15 British cohorts with access to 1H-NMR metabolomic data as well as genetic material and incident clinical events (totalling 35K participants with > 7K CVD events).

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Grant Details

Amount Awarded 642354
Applicant Surname Daniel
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2015-05-27T00:00:00+00:00
Financial Year 2014/15
Grant Programme: Title Sir Henry Dale Fellowship
Internal ID 107617/Z/15/Z
Lead Applicant Dr Rhian Daniel
Partnership Name Royal Society/Wellcome Trust Sir Henry Dale Fellowship
Partnership Value 642354
Planned Dates: End Date 2017-06-11T00:00:00+00:00
Planned Dates: Start Date 2015-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof John Edmunds