A genome-wide study of DNA methylation in white blood cells and asthma in Latino children and youth.

ABSTRACT

Latinos are heavily affected with childhood asthma. Little is known about epigenetic mechanisms of asthma in Latino youth. We conducted a meta-analysis of two epigenome-wide association studies (EWAS) of asthma, using DNA from white blood cells (WBCs) from 1,136 Latino children and youth aged 6 to 20 years. Genes near the top CpG sites in this EWAS were examined in a pathway enrichment analysis, and we then assessed whether our results replicated those from publicly available data from three independent EWAS conducted in non-Latino populations. We found that DNA methylation profiles differed between subjects with and without asthma. After adjustment for covariates and multiple testing, two CpGs were differentially methylated at a false discovery rate (FDR)-adjusted P < 0.1, and 193 CpG sites were differentially methylated at FDR-adjusted P < 0.2. The two top CpGs are near genes relevant to inflammatory signalling, including CAMK1D (Calcium/Calmodulin Dependent Protein Kinase ID) and TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains). Moreover, 25 genomic regions were differentially methylated between subjects with and without asthma, at Sidák-corrected P < 0.10. An enrichment analysis then identified the TGF-beta pathway as most relevant to asthma in our analysis, and we replicated some of the top signals from publicly available EWAS datasets in non-Hispanic populations. In conclusion, we have identified novel epigenetic markers of asthma in WBCs from Latino children and youth, while also replicating previous results from studies conducted in non-Latinos.