A*STAR Research Attachment Programme 2015

A*STAR Institutes, Singapore

Faculty of Medical and Human Sciences

Integrating genotypic variability mapping into the genome-wide association framework to enhance discovery of novel risk loci for complex diseases

Dr Stephen Eyre & Dr Sonia Davila

The Agency for Science, Technology and Research (A*STAR) in Singapore together with the University of Manchester is offering the opportunity to experience outstanding international PhD training in emerging areas of bioscience and medical research priority.

The A*STAR Research Attachment Programme (ARAP) enables students to spend two years in Manchester and two years in Singapore at a prestigious A*STAR Research Institute. Successful candidates will work with distinguished and renowned supervisors from A*STAR and Manchester, in vibrant research-intensive environments.

Genome-wide association studies (GWASs) have been tremendously successful in highlighting numerous genetic loci associated with complex diseases, such as rheumatoid arthritis (RA). GWASs primarily consider additive genetic effects and rely on large sample numbers to detect loci with moderate or weak effects. A new challenge is to interrogate GWAS loci in the context of non-additive effects (e.g. gene interactions) largely ignored in GWAS analysis, and relate these findings to plausible biological interactions.

In addition, since with many rarer complex genetic diseases it is often not always feasible to increase sample numbers, an innovative approach with the capacity to enhance the discovery of novel risk loci, by prioritising findings that have both a suggestively significant (e.g. <10-5) additive signal coupled to a significant non-additive signal could be extremely useful.

One promising approach is genome-wide variability mapping (vGWAS), with the ability to prioritise potentially interacting loci in a hypothesis free manner. vGWAS interrogates the statistical variability across all marker genotypes, gaining information of non-additive and environmental effects ignored in GWASs. The vGWAS method has been successfully applied to quantitative traits but is not directly applicable to diseases. We have therefore developed a pipeline that integrates vGWAS into the GWAS framework for studying diseases.

In this project, the successful candidate will use computer simulation to optimise the pipeline in a range of scenarios. This pipeline will be assessed in case studies of both a common and rare genetic disease, with confirmed susceptibility loci, for its effectiveness in detecting known loci from much reduced sample numbers in the discovery cohorts. In addition, we will attempt to assess the candidature of any novel risk loci identified in the case studies.

This 4-year full-time studentship provides full support for UK/EU tuition fees, training costs and an annual minimum tax-free stipend at RCUK rates (currently £13, 863). The project is due to commence October 2015 and is open to UK/EU nationals only due to the nature of the funding.

Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in a related medical, biological, statistical or mathematical science. A Masters degree in a similar discipline would be beneficial as would previous experience of some of the techniques referenced above.

Details on the application process and further information on the A*STAR-Manchester scheme can be found on our website:

www.singaporeastar.manchester.ac.uk/

Interested individuals are strongly recommended to contact Dr Eyre prior to submitting an application to establish suitability for the project as well as gain further information on the planned research (stephen.eyre<στο>manchester.ac.uk).

www.inflammation-repair.manchester.ac.uk/staff/80

Applications should be submitted online by 5pm, Friday 23 January 2015.