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Prof Jenny Barrett
Dr M Pujades-Rodriguez
Prof A Morgan
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Rheumatoid arthritis (RA), vasculitis and polymyalgia rheumatic (PMR) are related chronic inflammatory conditions. Glucocorticoid therapy is widely used in their treatment, sometimes leading to long-term toxicities, including cardiovascular disease, diabetes, osteoporosis and adrenal suppression. The proposed research will analyse the genetic correlations underlying the diseases and their comorbidities to better understand the inter-relationships between disease, treatment and comorbidity. This project is suitable for a student with a strong statistical background and an interest in developing and applying statistical skills to the area of genetics and health.
In the UK the prevalence of long-term prescription of glucocorticoids has increased over time despite the morbidity associated with their use. Surprisingly little is known about the incidence of different types of glucocorticoid toxicities and about the factors associated with their development. Current evidence originates primarily from clinical trials, which commonly include selected patients, not representative of the population receiving the medication, and the study duration rarely allows the investigation of long-term toxicities. In particular, it is not known what the incidence of cardiovascular disease, osteoporosis and adrenal suppression is in a real-world setting and what their predictors are. These toxicities can have a major impact on life expectancy, quality of life and on psychological wellbeing of patients, particularly in the elderly population, resulting in high personal and economic burden.
The proposed project will contribute to understanding the genetics of these traits and their comorbidities as part of a wider programme of research aimed at enabling clinicians and policymakers to balance harms and benefits of glucocorticoids for the treatment of RA, vasculitis (including giant cell arteritis) and PMR. The student will be part of a multidisciplinary research team with expertise in statistical genetics, electronic phenotyping and analysis of routinely collected medical data. The project is aligned with the MRC partnership TARGET, which is led by Ann Morgan, a rheumatologist and Professor of Molecular Rheumatology at the University of Leeds, who will co-supervise the project.
The PhD will be based on the analysis of UK Biobank data, which includes genome-wide genetic data on 500,000 subjects from the UK population and linkage to primary care, hospital admissions and mortality data. The team has approval for a programme of research to develop prognostic and economic models of longer-term complications of treatment in people with chronic inflammatory diseases.
The focus of the studentship will be on the application of statistical genetics techniques to describe the genetic correlation between the different inflammatory diseases and their comorbidities at a genome-wide level, and with focus on specific genetic regions (specifically the major histocompatibility complex). New methods will be used that are aimed at distinguishing between genuine pleiotropy (where two traits are each influenced by the same gene(s)) and apparent pleiotropy, where the genetic effects on one trait are mediated either directly by the other trait or by associated treatment. Power to identify predictors of response to glucocorticoids will be gained by carrying out these analyses across (related) diseases.
This PhD studentship will provide an excellent opportunity to develop skills in the analysis of genetic data and electronic health records, applied to important clinical questions. The research will be developed in the MRC Medical Bioinformatics Centre of Leeds, part of Leeds Institute for Data Analytics, that offers exciting opportunities for training, networking and career development in key strategic areas of growing importance (e.g. bioinformatics, design of record-linkage studies, statistical analysis, genetics, risk prediction and electronic phenotyping). The student will also spend time at the SME Pharmatics (http://www.pharmaticsltd.com), whose expertise is in machine learning applied to health, where they will have the opportunity to learn more about the workings of non-academic research organisations.
The ability to identify which patients are more likely to experience side effects from glucocorticoids could lead to targeted interventions to limit drug-related harm. It will also provide health economic justification for trials of alternative treatment strategies, and inform policy and the development of clinical guidelines.
In the UK the prevalence of long-term prescription of glucocorticoids has increased over time despite the morbidity associated with their use. Surprisingly little is known about the incidence of different types of glucocorticoid toxicities and about the factors associated with their development. Current evidence originates primarily from clinical trials, which commonly include selected patients, not representative of the population receiving the medication, and the study duration rarely allows the investigation of long-term toxicities. In particular, it is not known what the incidence of cardiovascular disease, osteoporosis and adrenal suppression is in a real-world setting and what their predictors are. These toxicities can have a major impact on life expectancy, quality of life and on psychological wellbeing of patients, particularly in the elderly population, resulting in high personal and economic burden.
The proposed project will contribute to understanding the genetics of these traits and their comorbidities as part of a wider programme of research aimed at enabling clinicians and policymakers to balance harms and benefits of glucocorticoids for the treatment of RA, vasculitis (including giant cell arteritis) and PMR. The student will be part of a multidisciplinary research team with expertise in statistical genetics, electronic phenotyping and analysis of routinely collected medical data. The project is aligned with the MRC partnership TARGET, which is led by Ann Morgan, a rheumatologist and Professor of Molecular Rheumatology at the University of Leeds, who will co-supervise the project.
The PhD will be based on the analysis of UK Biobank data, which includes genome-wide genetic data on 500,000 subjects from the UK population and linkage to primary care, hospital admissions and mortality data. The team has approval for a programme of research to develop prognostic and economic models of longer-term complications of treatment in people with chronic inflammatory diseases.
The focus of the studentship will be on the application of statistical genetics techniques to describe the genetic correlation between the different inflammatory diseases and their comorbidities at a genome-wide level, and with focus on specific genetic regions (specifically the major histocompatibility complex). New methods will be used that are aimed at distinguishing between genuine pleiotropy (where two traits are each influenced by the same gene(s)) and apparent pleiotropy, where the genetic effects on one trait are mediated either directly by the other trait or by associated treatment. Power to identify predictors of response to glucocorticoids will be gained by carrying out these analyses across (related) diseases.
This PhD studentship will provide an excellent opportunity to develop skills in the analysis of genetic data and electronic health records, applied to important clinical questions. The research will be developed in the MRC Medical Bioinformatics Centre of Leeds, part of Leeds Institute for Data Analytics, that offers exciting opportunities for training, networking and career development in key strategic areas of growing importance (e.g. bioinformatics, design of record-linkage studies, statistical analysis, genetics, risk prediction and electronic phenotyping). The student will also spend time at the SME Pharmatics (http://www.pharmaticsltd.com), whose expertise is in machine learning applied to health, where they will have the opportunity to learn more about the workings of non-academic research organisations.
The ability to identify which patients are more likely to experience side effects from glucocorticoids could lead to targeted interventions to limit drug-related harm. It will also provide health economic justification for trials of alternative treatment strategies, and inform policy and the development of clinical guidelines.
Funding Notes
This studentship is part of the MRC Discovery Medicine North (DiMeN) partnership and is funded for 3.5 years. Including the following financial support:
Tax-free maintenance grant at the national UK Research Council rate
Full payment of tuition fees at the standard UK/EU rate
Research training support grant (RTSG)
Travel allowance for attendance at UK and international meetings
Opportunity to apply for Flexible Funds for further training and development
Please carefully read eligibility requirements and how to apply on our website, then use the link on this page to submit an application: https://goo.gl/jvPe1N
Tax-free maintenance grant at the national UK Research Council rate
Full payment of tuition fees at the standard UK/EU rate
Research training support grant (RTSG)
Travel allowance for attendance at UK and international meetings
Opportunity to apply for Flexible Funds for further training and development
Please carefully read eligibility requirements and how to apply on our website, then use the link on this page to submit an application: https://goo.gl/jvPe1N
Project supervisors
Career overview
Professor Jenny Barrett is a biostatistician specialising in statistical genetics and has been a Professor of Statistical Genetics at the University of Leeds since 2011. She transitioned from the St James''s University Hospital campus to the Leeds Institute for Data Analytics in June 2018. Since 2000, she has led a statistical research group at the University, initially serving as a Cancer Research UK Genetic Epidemiologist and Honorary Principal Research Fellow, followed by roles as University Research Fellow, Reader in Biostatistics, and Genetic Epidemiology. Professor Barrett completed her undergraduate degree in Mathematics and Philosophy before working in secondary and adult education, as well as with the Open University, primarily teaching mathematics. She returned to higher education to pursue an MSc and PhD in statistics after her children started school. Her previous academic positions include Lecturer in Medical Statistics at the Arthritis Research Campaign Epidemiology Unit at the University of Manchester (1997-2000), Lecturer in Cancer Statistics at the University of Leeds (1996-1997), and Lecturer in Medical Statistics at the University of Leeds (1993-1995). While her broader interest lies in biostatistics, most of her research has concentrated on statistical genetics, particularly the genetic epidemiology of various complex diseases, including cancers, musculoskeletal diseases, and cardiovascular diseases.
Research interests
Professor Barrett''s research interests encompass several areas within statistical genetics and genetic epidemiology. She has led large-scale international genome-wide studies on melanoma susceptibility and familial melanoma, collaborating with the international melanoma genetics consortium GenoMEL. Additionally, her work includes the analysis of tumour transcriptomics related to prognosis as part of the MELGEN European Training Network. In the field of rheumatoid arthritis and giant cell arteritis, she has long-term collaborations focusing on the genetic epidemiology and pharmacogenetics of these conditions, particularly studying the FC-gamma receptor region. She co-leads the analysis workstream for the national MATURA consortium, which aims to identify genetic predictors of therapy response in rheumatoid arthritis patients. Furthermore, she has contributed to genome-wide association studies of giant cell arteritis and is involved with the MRC Target consortium, which seeks to reduce steroid toxicity and improve patient outcomes. Professor Barrett is also engaged in clinical research projects related to colorectal cancer, focusing on discovering biomarkers of treatment response in advanced cases, and is aligned with the UK Colorectal Cancer Intelligence Hub CORECT-R. Her methodological research includes developing and refining statistical approaches relevant to her applied studies, covering family-based genetic studies, genetic association investigations, transcriptomic data analysis, risk modelling, and predictive biomarker studies.
Statistical Genetics
Genetic Epidemiology
Biostatistics
Melanoma Research
Epidemiological Studies
Pharmacogenetics
Biomarker Studies
Rheumatoid Arthritis
Giant Cell Arteritis
Colorectal Cancer
Genome-Wide Association Studies
Family-Based Genetic Studies
Transcriptomic Data Analysis
Risk Modelling
Predictive Biomarker Studies.
Dr M Pujades-Rodriguez's profile is coming soon
View other supervisors at University of LeedsCareer overview
Professor Ann Morgan is the Head of the Molecular and Personalised Medicine Group within the Leeds Institute of Cardiovascular and Metabolic Medicine. She graduated from the University of Leeds with first class honours in Pathology and a Bachelor of Medicine and Surgery with Honours, achieving distinctions in Biochemistry and Surgery, as well as prizes in Medicine and Surgery. Professor Morgan chose a clinical career in rheumatology and subsequently undertook a PhD studying Fc gamma receptor genetics in rheumatoid arthritis, supported by an MRC Clinical Training Fellowship. She continued her research in Fc gamma receptor biology during an Arthritis Research UK/Academy of Medical Sciences Clinician Scientist Fellowship. The award of her HEFCE Clinical Senior Lectureship allowed her to continue her work on Fc gamma receptors while developing new academic interests in genetic and soluble biomarkers and disease outcomes. Her main clinical interests include vasculitis and rare autoimmune diseases, and she leads the regional Behçet''s syndrome and large vessel vasculitis services. Professor Morgan''s active research projects range from laboratory studies to large data analysis and patient-focused research. She chairs both the UK GCA Consortium and the MRC TARGET Partnership and is establishing an expanding research programme in vascular biology. In addition to her academic responsibilities, she serves as the Academic Training Programme Director for Rheumatology and as a Consultant Rheumatologist. Professor Morgan has supervised numerous students at various academic levels and welcomes enquiries from motivated and qualified applicants interested in PhD study in her field. Her research interests encompass interdisciplinary projects that explore the genetic determinants of autoimmune diseases and the development of clinically useful diagnostic, prognostic, and predictive biomarkers.
Research interests
Professor Morgan''s research focuses on rheumatology, particularly in the areas of vasculitis, giant cell arteritis, polymyalgia rheumatica, Behçet’s syndrome, rheumatoid arthritis, and genetics. She leads interdisciplinary projects that investigate the role of autoantibodies in persistent inflammatory responses and has identified novel genetic variants in IgG receptors associated with autoimmune diseases. Her work includes the development of therapeutics, such as Affimers, aimed at treating rheumatoid arthritis and other autoantibody-mediated diseases. Professor Morgan collaborates with national and international genetics consortia and rare disease communities to translate genetic discoveries into clinically useful biomarkers. Her research includes the MRC TARGET programme, which aims to reduce glucocorticoid toxicity and improve outcomes for patients with giant cell arteritis through enhanced clinical evaluation tools. She also leads the UK GCA Consortium, which investigates genetic determinants of giant cell arteritis and polymyalgia rheumatica susceptibility. Additionally, she is involved in the HELICAL Innovative Training Network, focusing on the analysis of large datasets from individuals with vasculitis, and aims to identify key pathogenic pathways for therapeutic targeting in giant cell arteritis. Professor Morgan''s research encompasses laboratory studies, large data analysis, and patient-focused research, contributing significantly to the understanding and treatment of autoimmune diseases.
Rheumatology
Vasculitis
Giant Cell Arteritis
Polymyalgia Rheumatica
Behçet’s Syndrome
Rheumatoid Arthritis
Genetics
Fc Gamma Receptors
Autoimmune Diseases
Molecular Medicine
Personalised Medicine
Biomarkers
Drug Development
Clinical Research
Genetic Variants
Inflammatory Responses
Patient-Focused Research
Interdisciplinary Collaboration
Therapeutic Targeting
Clinical Evaluation
Prognostic Biomarkers
Glucocorticoid Toxicity
Disease Outcomes
Rare Diseases
Academic Training
PhD Supervision
Research Grants
Autoantibodies
Data Analysis.
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