Projects per year
Abstract
Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N = 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.
Original language | English |
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Article number | 100544 |
Number of pages | 19 |
Journal | Cell Genomics |
Volume | 4 |
Issue number | 5 |
Early online date | 30 Apr 2024 |
DOIs | |
Publication status | Published - 8 May 2024 |
Bibliographical note
Publisher Copyright:© 2024 The Authors
Research Groups and Themes
- ICEP
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Dive into the research topics of 'Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts'. Together they form a unique fingerprint.Projects
- 1 Active
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8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M. (Principal Investigator)
1/10/20 → 30/09/25
Project: Research