Poster Presentation GENEMAPPERS 2024

Investigating the Role of Medication and Inflammation in Frailty with Polygenic and Epigenetic Data (#105)

Jonny Flint 1 2 3 4 , Miles Welstead 5 , Tom Russ 4 , Alan Marshall 2 6 , Nick Martin 1 , Simon Cox 3 7 , Michelle Luciano 3 7 , Michelle Lupton 1
  1. Brain and Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  2. Advanced Care Research Centre, School of Engineering, College of Science and Engineering, University of Edinburgh , Edinburgh , Scotland, UK
  3. Lothian Birth Cohorts, Department of Psychology , University of Edinburgh , Edinburgh , Scotland, UK
  4. Alzheimer Scotland Dementia Research Centre, University of Edinburgh , Edinburgh , Scotland, UK
  5. , Scottish Brain Sciences, Edinburgh , Scotland, UK
  6. School of Social and Political Science, University of Edinburgh , Edinburgh , Scotland, UK
  7. Department of Psychology , University of Edinburgh , Edinburgh , Scotland, UK

Our previous analysis has found that a polygenic risk score (PRS) for rheumatoid arthritis (RA) is protective against frailty. One possible mediation pathway could be the role of anti-inflammatory drugs that people with RA may be taking. “Inflammaging” has been the term used to explain the relationships between chronically raised inflammatory biomarkers that are associated with biological aging and frailty. Some evidence has demonstrated that anti-inflammatory medications may lower levels of inflammatory biomarkers - leading one to theorise that such medications should lower risk of frailty. However, there is limited data on the association between anti-inflammatory medications and frailty. For example, long-term aspirin use was associated with a 15% lower risk of frailty. Other research has found contradicting findings – such as long-term nonsteroidal anti-inflammatory agent (NSAID) medication use being associated with an increased prevalence of frailty, even after consideration of multimorbidity. Given our previous findings and that the literature to date is mixed, we analyse the role of anti-inflammatory drugs and pathways (represented via protein markers and epigenetic scores) as mediators to explore the role of anti-inflammatory medication and inflammatory pathways on frailty - longitudinally in ~1005 older adults in the Lothian Birth Cohort 1936 (LBC1936), Scotland (UK), and in ~3068 adults aged 40-80 years in the Prospective Imaging Study of Ageing (PISA), Australia. Initial findings reveal the role of inflammation and pain medication as a moderator in the relationship between the rheumatoid arthritis PRS and frailty status. The epigenetic pathway analyses reveal a strong relationship between medication usage, L-Selectin expression and frailty. Further analysis, including pairwise GWAS comparison, are being conducted to explore shared biological pathways between rheumatoid arthritis and frailty. Results could help understand the role of medication and inflammation in the development of frailty and provide new evidence for the pathways involved in reducing frailty levels.