B3669 - Exploring epigenetic and phenotypic associations with genetic liability to juvenile idiopathic arthritis - 02/12/2020

B number: 
B3669
Principal applicant name: 
Gemma Sharp | MRC IEU, UoB
Co-applicants: 
Dr Sarah Clarke
Title of project: 
Exploring epigenetic and phenotypic associations with genetic liability to juvenile idiopathic arthritis
Proposal summary: 

Juvenile idiopathic arthritis (JIA) is the most common rheumatic condition of childhood, but remains a relatively rare condition. Whilst there is growing knowledge about JIA disease management, we have very limited knowledge about the wider impacts of the condition, particularly in adolescence and adult life. For example observational data suggests that JIA patients have adverse educational attainment levels and employment outcomes. There is also growing concern about wider health implications of JIA such as cardiovascular disease risk, similar to that seen for adult rheumatoid arthritis patients, although long term follow-up data of JIA patients into adulthood is very limited. Within this PhD a range of different techniques are being used to explore causes and effects of JIA across the life course using observational and ‘omic data. Our earlier work has shown associations between JIA and a number of other health outcomes, however outcome datasets have all derived from older adult populations. Building on earlier work, this project aims to examine the association between the level of the genetic risk of JIA (using polygenic risk scoring) and a range of clinical (e.g. cardiovascular risk factors), biological (e.g. circulating CRP levels), metabolic (eg circulating lipids) and molecular (e.g. changes to DNA methylation) outcomes during childhood and early adulthood. This will allow us to identify potential JIA associated comorbidity earlier in disease to a) allow earlier risk stratification of patients and b) allow underlying mechanisms of comorbidity to be explored.

Impact of research: 
Understanding the wide health impact of JIA on patients with the condition will enable a more targeted and holistic approach to their care with regards to risk stratification and modification. This will be particularly important as JIA patient transition from paediatric to adult health services.
Date proposal received: 
Monday, 30 November, 2020
Date proposal approved: 
Wednesday, 2 December, 2020
Keywords: 
Epidemiology, Juvenile Idiopathic Arthritis, EWAS, pheWAS, Childhood - childcare, childhood adversity, Epigenetics, Genetic epidemiology, Mendelian randomisation