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PhD In Cancer & Genetics - Identifying genetic modifiers of age of cancer onset

  • Full or part time
    Prof J P Cheadle
    Prof V Escott-Price
  • Application Deadline
    Wednesday, February 27, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Rare highly penetrant genetic disease alleles cause early disease onset. In some conditions such as Huntington’s chorea, the size of the disease causing allele directly affects age of onset. Beyond known high penetrance and low pentrance risk alleles, we hypothesize that alleles may exist that affect age of disease onset, but not necessarily risk. We will explore this possibility for cancer by utilising age of onset data from the COIN trial consisting of >2,200 patients with advanced colorectal cancer. We have genome wide genotyping data on over 10 million common and rare polymorphic variants for each patient and the student will use this data to seach for alleles that modify age of onset via a genome wide association study. We will perform similar analyses on up to 78,000 patients with cancer from the UK Biobank. We will cross validate and carry out meta-analyses to identify and validate genetic biomarkers. The student will subsequently search for clinical and lifestyle factors which may correlate with age of onset – to help determine underlying causes and potential mechanisms. We will expand the analyses to other non-cancer diseases to identify associations of multimorbidity. This project has multiple avenues to be followed and will allow the student to develop creative free thinking by identifying genetic modifiers across multiple cancer types and to work out their potential mechanisms by designing and performing both stratification analyses and also in silico functional analyses. Identification of genetic biomarkers has the potential to inform patient surveillance, outcome and management.

This is a computer-based statistical analysis project in which programming in R or Python will be essential (can be taught if necessary). The student will gain a wide range of expertise in computer based biostatistics and bioinformatics (Pearson chi-square test, Cox survival model, Bonferroni correction, multiple fractional polynomial model, fixed-effects inverse-variance meta-analysis and Q & I-squared statistics, and, analyses using Polyphen and Align-GVGD, and, expression, transcription factor binding site and chromatin localisation data from ENCODE).

We seek a candidate holding, or expected to gain, a 1st or 2:1 honours degree in either (i) a biological science with a strong interest in statistics / mathematics / high performance computing, or, (ii) computer science, with a strong interest in its statistical application to biology / healthcare. Cheadle and Escott-Price will oversee the student’s studies; their groups have substantial expertise in identifying disease susceptibility alleles, and, alleles that affect prognosis. Cheadle and Escott-Price have successfully supervised >20 Ph.D. students, and the majority of their students have published first author REF-returnable papers.

Funding Notes

The studentship is generously funded by the School of Medicine
Full UK/EU tuition fees
Doctoral stipend matching UK Research Council National Minimum
Additional funding is available over the course of the programme and will cover costs such as research consumables and training.
Applicants should possess a minimum of an upper second class Honours degree, master's degree, or equivalent in a relevant subject.
Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS)

References

In order to be considered you must submit a formal application via Cardiff University’s online application service. (To access the system click 'Apply Online' at the bottom of this advert)
There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (October 2019). This will take you to the application portal.

Candidates are only permitted to submit one application but may select a maximum of three projects, ranked in order of preference in the ‘Research Proposal’ section of the application. In order to be considered candidates must submit the following information:
• Supporting statement
• CV
• Qualification certificates
• References x 2
• Proof of English language (if applicable)

Related Subjects

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