Data Entry Maintenance

Metadata Commons Identifier

HMC000098

Project Title

Accelerated Epigenetic Aging Worsens Survival And Mediates Environmental Stressors In Fibrotic Interstitial Lung Disease

Project Description

Background The role of epigenetic aging in the environmental pathogenesis and prognosis of fibrotic interstitial lung disease (fILD) is unclear. We evaluated whether ambient particulate matter ≤2.5 μm (PM2.5) and neighbourhood disadvantage exposures are associated with accelerated epigenetic aging, and whether epigenetic age is associated with adverse clinical outcomes in patients with fILD.Methods This multicentre, international, cohort study included patients with fILD from the University of Pittsburgh (UPitt, n=306) and University of British Columbia (UBC, n=170). Five-year PM2.5 exposures were estimated using satellite-derived models. Neighbourhood disadvantage was calculated using U.S. and Canadian Census-based metrics. Epigenetic age difference (EAD=epigenetic age – chronological age) was calculated using GrimAge analysis of blood DNA methylation data. Linear models assessed associations of exposures with EAD. Cox models assessed associations of EAD with transplant-free survival. Causal mediation analysis evaluated EAD mediation of exposure-survival relationships.Results Median epigenetic age was 11.7 years older than chronological age in patients with fILD. In combined cohort analysis, each interquartile range (IQR) PM2.5 increase was associated with 2.88 years (95%CI 1.39–4.38, p<0.001) increased EAD. In UPitt, each IQR neighbourhood disadvantage increase was associated with 1.16 years (95%CI 0.22–2.09, p=0.02) increased EAD. Increased EAD was associated with worse transplant-free survival (HR=1.17 per 1-year increase EAD, 95%CI 1.10–1.24, p<0.001), with EAD mediating 40% of PM2.5-survival relationship and 59% of neighbourhood disadvantage-survival relationships. Epigenetic age was also more strongly associated with transplant-free survival than chronological age.Conclusions Epigenetic age acceleration is associated with worse survival and mediates adverse exposure impacts in fILD.This study is related to Genome BC DIA001 project (<a href="https://metadatacommons.ca/ords/r/genomebc/hmc/data-entry-maintenance-ro?p18_id=32526669869472710567863186804110442434&p18_last_page=2&p18_cohort_id=32526669869473919493682801433285148610&clear=18&session=2929492360910&cs=1ClhaQabW7pXE5TvtHZe_fwnES8ZIiM2-w3Iyu9-UKVm5cYhsXwMjcgP_M1TRGPb_q7GA_v9VE0uCscpyKpdqvg">HMC000049</a>)

Project Funder(s)

Genome British Columbia, Boehringer Ingelheim

Project Institution(s)

University of British Columbia, Centre for Heart Lung Innovation, University of Pittsburgh, University of Chicago, McGill University, University of Nottingham, Queens University, University of Calgary

Data Access Request URL*

Keywords

Epigenetic age, Air pollution, Transplant free survival

Publication Link

https://pubmed.ncbi.nlm.nih.gov/39884761/

Study Completed

Cohort Name

Multicentre, international, cohort study of patients with fILD

Cohort Size

476

Disease/Condition Studied

interstitial lung disease

Enrollment Time Window

2000-2022

Biobanking Consent Available

Medical History Available

Ethnicity Availability

Time Course

Patient Phenotypes

accelerated aging

Patient Outcomes

fILD and other aging-related diseases

Clinical Data Types Available

smoking history, forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) values collected throughout the duration of registry enrollment

Time Course Data Points

Enrollment City

Groups

Project

Cohort

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Samples and Omics