PhD: Classifying Mechanisms of Pleiotropy To Improve Causal Modelling

University of Bristol - Faculty of Health Sciences/Bristol Medical School

The project:

A decade of genome wide association studies (GWAS) has resulted in thousands of genetic variants known to associate with traits across the human phenome. With this resource comes the hope of a profound improvement in the drug discovery process, specifically by increasing the safety of new drugs and lowering their development costs. Mendelian randomisation (MR) is an experimental design that uses genetic associations with a putative 'exposure' phenotype to infer its causal effect on an 'outcome' phenotype of interest. Using known genetic associations in this fashion has proven to be effective at predicting the chance that a drug target (exposure) is likely to be effective for an outcome. It is now possible to construct causal networks of thousands to tens of thousands of molecular phenotypes that might aid in prioritising those molecular targets most likely to be causally influencing human physiology.

Aims & Objectives

  1. Overlay causal insights with fine mapping and known metabolic pathways to characterise the nature of genetic pleiotropy.
  2. Develop more reliable causal models that incorporate prior information about distributions of pleiotropic effects or specific knowledge about pleiotropic actions on specific SNPs.
  3. Using genetic associations for multiple ’omic datasets, apply newly developed MR methods to predict the safety and efficacy of existing and completed drug trials.

Environment:

The student will be supervised by Prof George Davey Smith (University of Bristol), Dr Gibran Hemani (University of Bristol), Tom Gaunt (University of Bristol), Dr Matt Nelson (GSK), and Dr Robert Scott (GSK). The student will be based primarily at the MRC Integrative Epidemiology Unit, University of Bristol. The student will also spend time embedded at the GlaxoSmithKline Research and Development Centre in Stevenage to gain industry experience.

How to apply:

Please make an online application for this project at http://www.bris.ac.uk/pg-howtoapply. Please select 'Faculty of Health Sciences/Social Medicine PhD' on the Programme Choice page. Under Funding, identify `BBSRC funded PhD`as your fee payer. Under Research Details, provide the names of all project supervisors listed above.

Please provide a current CV, covering letter, certified copies of degree certificates and transcripts, and two academic references.

Only applicants from the UK/EU are eligible for this programme.

Closing date: 5pm, 26th September 2017, Interviews: 28th September 2017.

Important: Please note the central application system will be closed from 15th-26th September 2017. If you wish to apply between those dates please send your CV/covering letter/copies of certificates and transcripts with details of referees to Sharen.okeefe@bristol.ac.uk.

Closing date: 5pm, 26th September 2017.

Funding: University of Bristol/BBSRC 4 year funded PhD.

Contacts: Gibran Hemani g.hemani@bristol.ac.uk.

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Type / Role:

PhD

Location(s):

South West England