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(MRC DTP) Improved classification of myositis disease subtypes using statistical genetics approaches for stratified medicine


Project Description

Keywords: idiopathic inflammatory myopathy, myositis, genetics, disease classification, stratified medicine

Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases characterized by inflammation of skeletal muscle (myositis). Other organ involvement due to lung, heart and skin disease and cancers can lead to increased mortality. IIM is difficult to diagnose, classify and treat; many patients are permanently disabled due to irreversible muscle damage. Improved disease classification in IIM is vital to stratify patients to improve disease management and enable earlier, more targeted treatment.

In this PhD project, we aim to improve disease classification and characterise disease subtypes in IIM. We aim to identify genetic risk factors that differentiate disease subgroups; to investigate similarities and differences in genetic risk factors between IIM and related immune-mediated inflammatory disorders, and to use publically available genetic and genomic data to increase understanding of different types of myositis.

We will use a number of statistical genetics approaches to exploit our wealth of clinical, genetic, genomic and autoantibody data to improve patient stratification. These approaches may include polygenic risk score analysis, conditional false discovery leveraging other autoimmune diseases, meta-analyses, Mendelian randomization, machine learning and integrated multi-omics approaches.

We expect these analyses to improve disease classification and our ability to stratify patients in IIM. This may improve our understanding of the pathogenesis and disease mechanisms in different forms of IIM. This research also will improve the evidence-base for stratified medicine, leading to more focussed disease management and treatment.

The student will be integrated into an active research group within the Versus Arthritis Genetics and Genomics Centre of Excellence. Training will be provided in quantitative statistical genetics skills, and interdisciplinary skills in translational and stratified medicine. There will be opportunities to attend and present results at national and international meetings and conferences, and public and patient engagement events.

Manchester Myositis Research Group:
http://www.research.manchester.ac.uk/portal/en/projects/the-manchester-myositis-research-group(b9369a1a-b679-4b53-9e10-a66f7a7ee134).html

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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