Determining the biological basis of observed clinical outcomes in juvenile idiopathic arthritis using genetics and multiomics


   Faculty of Biology, Medicine and Health

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory arthritis affecting children and young people with an age of disease onset less than 16 years of age. The clinical symptoms of JIA are very heterogeneous which has led to the development of classification systems to help define homogenous subgroups. The classification systems include the International League of Associations for Rheumatology (ILAR) criteria and, more recently, the Pediatric Rheumatology International Trials Organization (PRINTO) guidelines. These classification guidelines use clinical outcomes such as age of disease onset and antinuclear antibody (ANA) to define the subgroups. While these guidelines are helpful to define subgroups for research purposes, little is known about the biological and molecular processes that lead to these observed clinical outcomes.

This project will use genetic and clinical data collected in large cohorts of patients with JIA to identify genetic variants, genes and biological pathways that are linked with clinical outcomes. In addition, the project will analyse proteomic datasets in the same patients to help further understand the biology, identify biomarkers and contribute to the molecular taxonomy of JIA. The research will be conducted as part of the Manchester Children’s and Young people’s Rheumatology Research Programme (CHYRRP) within the Centre of Musculoskeletal Research at the University of Manchester. CHYRRP is a network of clinicians, academics and researchers with expertise in rheumatology, genetics, data science, epidemiology and statistics focused on addressing key research questions in JIA. 

Training/techniques to be provided

The student will be integrated into an interdisciplinary and active research group at the Manchester Children and Young Persons Rheuamatology Research Programme (CHYRRP), part of the Centre for Musculoskeletal research (CfMR). The student will attend regular lab meetings and journal clubs, covering epidemiology, genetics, functional genomics, and bioinformatics. The student will also present at CHYRRP and CfMR seminars to gain experience in formal presentations. Training in quantitative skills (statistics, data analytics and bioinformatics) and “big-data” handling will be provided by the supervisory team. Additional training and skills development opportunities will be provided through attendance and presentation of results at national and international conferences, such as the British Society for Rheumatology Paediatric meeting. The student will attend in-house training courses in Epidemiology, Genetics and Biostatistics.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum 2.1 (or equivalent) in epidemiology, statistics, data science. computing or relevant subject area. A masters degree is relevant subject area and/or experience in a related area/discipline is desirable. Candidates with an interest in health informatics, genetics or statistics are encouraged to apply.

How to Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD Genetics.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Equality, Diversity & Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

Biological Sciences (4) Computer Science (8) Mathematics (25) Medicine (26)

Funding Notes

Applications are invited from self-funded students. This project has standard fees. Details of our different fee bands can be found on our website View Website

References

1. López-Isac E, Smith SL, Marion MC, Wood A, Sudman M, Yarwood A, Shi C, Gaddi VP, Martin P, Prahalad S, Eyre S, Orozco G, Morris AP, Langefeld CD, Thompson SD, Thomson W, Bowes J. Combined genetic analysis of juvenile idiopathic arthritis clinical subtypes identifies novel risk loci, target genes and key regulatory mechanisms. Ann Rheum Dis. 2021 Mar;80(3):321-328. doi: 10.1136/annrheumdis-2020-218481.
2. Gurke R, Bendes A, Bowes J, Koehm M, Twyman RM, Barton A, Elewaut D, Goodyear C, Hahnefeld L, Hillenbrand R, Hunter E, Ibberson M, Ioannidis V, Kugler S, Lories RJ, Resch E, Rüping S, Scholich K, Schwenk JM, Waddington JC, Whitfield P, Geisslinger G, FitzGerald O, Behrens F, Pennington SR; HIPPOCRATES Consortium. Omics and Multi-Omics Analysis for the Early Identification and Improved Outcome of Patients with Psoriatic Arthritis. Biomedicines. 2022 Sep 24;10(10):2387. doi: 10.3390/biomedicines10102387.
3. Beesley RP, Hyrich KL, Humphreys JH. The incidence and prevalence of Juvenile Idiopathic Arthritis differs between ethnic groups in England. Rheumatology (Oxford). 2023 Dec 22:kead700. doi: 10.1093/rheumatology/kead700.
4. Costello RE, Kearsley-Fleet L, McDonagh JE, Hyrich KL, Humphreys JH. Continuing specialist care into adulthood in young people with juvenile idiopathic arthritis: a retrospective cohort study using electronic health records in England. Rheumatology (Oxford). 2023 May 2;62(5):1936-1943. doi: 10.1093/rheumatology/keac497.
5. Costello R, McDonagh J, Hyrich KL, Humphreys JH. Incidence and prevalence of juvenile idiopathic arthritis in the United Kingdom, 2000-2018: results from the Clinical Practice Research Datalink. Rheumatology (Oxford). 2022 May 30;61(6):2548-2554. doi: 10.1093/rheumatology/keab714.

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