The Unit is offering an exciting opportunity to work on Chronic thromboembolic pulmonary hypertension which is thought to represent the extreme consequences of the failure to resolve pulmonary embolism (PE). The underlying causes are not known. Though there is a defined genetic contribution to PE, it is not clear if this further predisposes to CTEPH, or whether there are alternative genetic contributors to CTEPH distinct from those known in PE. CTEPH occurs in 2-4% of patients with PE and does not have a Mendelian genetic inheritance and therefore any genetic contribution is likely to be polygenic common variation. We therefore have established the first multi-centre international GWAS in CTEPH to clarify the underlying genetic architecture inform pathophysiology and potentially identify risk factors for screening populations of patients post-PE.
We have collected a UK-based discovery cohort and an international validation cohort. This collection is expected to be on-going longer term beyond the established timelines of the post. DNA will be genotyped on the Illumina HumanOmniExpressExome microarray and control samples from a normal healthy ethnically matched UK population of 1500 individuals from the UK Blood Services Wellcome Trust Case Control Consortium (WTCCC) on the same Illumina platform. To identify and clarify causal variants in linkage disequilibrium (LD) with strongly associated variants we will undertake imputation of additional variants and fine mapping techniques. It is unlikely that the associated SNP polymorphic variants are pathogenic themselves, and therefore it is crucial to impute additional genotypes that are not included on the genotyping array using suitable large reference panels, publically available or available to our network (i.e. 1000 Genomes project, UK10K, UK BioBank or BRIDGE) and in disease comparator studies in VTE/PE cohorts through collaboration (Dr David Tregouet, INSERM, Paris). We will also have the ability to compare common variation with additional available WGS data in the Bridge and BHF funded UK COHORT in Idiopathic and Heritable PAH studies and parallel clinical datasets are also available on both CTEPH and IPAH cohorts on the Openclinica platform.
The statistician is required to perform post-imputation analyses on the above datasets, co-ordinate with collaborators and present the data at international meetings. It is our expectation that the data should be publishable within the lifecycle of the post.
You will have a PhD (or equivalent) in statistics, or a relevant discipline; computing experience, both of statistical packages (e.g. R) and experience in GWA studies. You must have good communication skills and be able to contribute substantially to writing scientific papers.
Fixed-term: The funds for this post are available for 1 years in the first instance.
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The closing date for applications is Thursday 9th August 2018 and interviews are yet to be confirmed.
Please quote reference SL16152 on your application and in any correspondence about this vacancy.
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