Abstract
Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication.
Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.
Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics.
Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate,
Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis.
Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.
Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics.
Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate,
Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 321 - 336 |
| Number of pages | 16 |
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 206 |
| Issue number | 3 |
| Early online date | 10 May 2022 |
| DOIs | |
| Publication status | Published - 1 Aug 2022 |
Bibliographical note
Funding Information:Supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01-ES043012). Infrastructure for the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium is supported in part by the National Heart, Lung, and Blood Institute (HL105756). Additional study-specific funding statements can be found in the online supplement.
Publisher Copyright:
© 2022 by the American Thoracic Society.