We have a 4-year PhD studentship funded by Cancer Research UK available to start in October 2010 which is to be awarded competitively to the best student applying to the Cancer Research UK Centre in Leeds. The studentship is open to UK/EU students and will provide a stipend and full fees. Interested applicants should have, or expect to gain, a good first degree (first or upper second class) in a relevant subject. Projects will be advertised until 31st July and shortlisting and interviews conducted in August.
The project proposed by the Genetic Epidemiology group (within the Section of Epidemiology and Biostatistics at the University of Leeds) concerns the identification of genetic association with disease when sampling from multiple populations. Supervisors will be Mark Iles ([log in to unmask]) and Jenny Barrett ([log in to unmask])
The PhD project requires someone with a degree in a numerate subject (such as Mathematics or Computing) and will involve a large degree of programming, although previous experience in this is not required. Informal enquiries may be addressed to the supervisors at the above email addresses.
Details of the Project
In the last few years studies aiming to locate those genetic factors that influence disease risk have focussed on common genetic variants with a small effect on risk. Such variants may increase risk by only a small amount, but are of public health importance as they may be carried by more than half the population. Such studies typically require samples of several thousand cases and controls, which in turn often leads to the use of samples from multiple populations. This approach has led to the discovery of over 100 genetic variants influencing the risk of diseases such as breast cancer, melanoma, heart disease, diabetes and rheumatoid arthritis as well as variants that influence traits such as height, weight and hair colour.
Such studies have also shown there to be subtle genetic differences between even neighbouring countries (such as France and Belgium). Thus if populations are represented in different frequencies in the case and control samples, such slight genetic differences may appear to be related to disease risk. These ethnic strata may be revealed by the application of principal components analysis (PCA). Adjusting for PCs at the analysis stage apparently solves the problem of ethnic differentiation. But this may come at a price.
The aim of this project is to study the efficacy of PCA and how it is affected by different sample collection strategies. For example the degree of uneveness of sample collection across countries, the use of a large set of publically-available genetic data from a single population, the inclusion of individuals from countries with very mixed genetic backgrounds such as the USA may all impact on the power and appropriateness of such analyses.
Our group has a particular interest in melanoma and we lead the analysis of a genome-wide association study of melanoma utilising data on thousands of individuals from multiple locations across Europe. Both genetic risk factors (such as pigmentation) and non-genetic risk factors (such as UV exposure) for melanoma vary in frequency across Europe and so might affect both the sampling of cases and the analysis that might be applied to these data. Thus we have a practical interest in such research and would expect these data to both inform the project and make use of the research results.
Mark Iles
Section of Epidemiology and Biostatistics,
Cancer Genetics Building
Cancer Research UK Clinical Centre,
St James's University Hospital,
Beckett Street,
Leeds,
LS9 7TF
UK
e-mail: [log in to unmask]
http://www.personal.leeds.ac.uk/~medimm/
phone: +44 (0)113 206 6607
fax: +44 (0)113 234 0183
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