Epigenome-wide association study of paediatric asthma in African Americans

Abstract

<b>Introduction:</b> Asthma affects African Americans disproportionally. Although the contribution of DNA methylation (DNAm) to asthma has been explored, epigenome-wide association studies (EWAS) in African Americans are scarce. <b>Aim:</b> To identify CpG sites and processes with differential methylation patterns in whole blood associated with asthma in African American children. <b>Methods:</b> We performed an EWAS in 250 patients with asthma and 233 healthy subjects from the Study of Asthma, Genes and the Environment (SAGE). Whole-blood DNAm was profiled with the Illumina EPIC array. The association of DNAm at 802,185 CpGs and asthma was tested via robust linear regression models adjusted by age, sex, ancestry, and tissue heterogeneity. An empirical genome-wide significance threshold of p&lt;9x10^-8 was adopted and enrichment analysis was performed for probes with a false discovery rate (FDR)&lt;5%. <b>Results:</b> Participants’ mean age was 15.1±3.9 years, and 49.7% were females. Nine CpGs were genome-wide significantly associated with asthma, which were annotated to genes participating in airway remodelling, inflammation, immunoregulation, and corticosteroid response (e.g., <i>CCL4</i>, <i>MAPK1</i>, <i>GLCCI1</i>, and <i>GRAMD3</i>). Based on 154 probes with FDR&lt;5%, significant enrichment was found for chemokine signalling pathway, viral protein interaction, and previous EWAS associations, such as smoking, nitrogen dioxide, and fractional exhaled nitric oxide. <b>Conclusions:</b> We identified several DNAm markers associated with paediatric asthma among African Americans related to key asthma processes and environmental exposures. Supported by NIH R01HL155024, R01MD010443, R56MD013312 and MCIN/AEI/10.13039/501100011033 PID2020-116274RB-I00.