Lung function epigenetic markers across the lifespan

<bold>BACKGROUND:</bold> Chronic Obstructive Pulmonary Disease (COPD) can have its origins in early life, and epigenetic mechanisms may be involved. This study investigates if lung function levels are associated with epigenetic profiles across the lifespan. <bold>METHODS:</bold> The association of FEV1(L) with epigenetic profiles (CpGs) was explored using linear models adjusting for age, sex, height, smoking status, pack-years, and blood cell counts. CpGs were meta-analyzed, across CADSET cohorts, with a fixed-effects model (metafor). They included children (0–12 years, n=1658), adolescents (13–20 years, n=542), young adults (21–40 years, n=876), adults (41–60 years, n=1933), and older adults (61–80 years, n= 1913). CpGs were annotated using Illumina database for gene mapping and genes were compared between age groups. <bold>RESULTS:</bold> We identified associations between FEV1 and methylation levels [VJ1] in 251 genes (p < 5 × 10⁻⁴) in the meta-analysis of adults aged 61–80 years. Significant associations between FEV1 and 30 of these genes were also found in at least one younger group. Functional enrichment revealed that these genes are involved, in part, in immune cell activation, regulation of hematopoiesis and leukocyte cell-cell adhesion. Additionally, some of the genes shared between adults 61-80 years old and children or adolescents have been previously linked to lung function decline in adults and prenatal exposure to maternal smoking (PTPRN2), DLCO in COPD patients (HDAC4) or to emphysema distribution (TRAPPC9). <bold>CONCLUSIONS:</bold> We identified associations between FEV1 across the lifespan and methylation levels at multiple annotated genes. The methylation levels of these genes could serve as potential early biomarkers of abnormal lung function later in life.