eQTM catalogue in children's blood

Background: The identification of expression quantitative trait
methylation (eQTMs), defined as associations between DNA methylation
levels and gene expression, might help the biological interpretation of
epigenome-wide association studies (EWAS). We aimed to identify autosomal
cis eQTMs in children’s blood, using data from 832 children of the Human
Early Life Exposome (HELIX) project. Methods: Blood DNA methylation and
gene expression were measured with the Illumina 450K and the Affymetrix
HTA v2 arrays, respectively. The relationship between methylation levels
and expression of nearby genes (1 Mb window centered at the transcription
start site, TSS) was assessed by fitting 13.6 M linear regressions
adjusting for sex, age, cohort, and blood cell composition. Results: We
identified 39,749 blood autosomal cis eQTMs, representing 21,966 unique
CpGs (eCpGs, 5.7% of total CpGs) and 8,886 unique transcript clusters
(eGenes, 15.3% of total transcript clusters, equivalent to genes). In
87.9% of these cis eQTMs, the eCpG was located at <250 kb from
eGene’s TSS; and 58.8% of all eQTMs showed an inverse relationship between
the methylation and expression levels. Only around half of the autosomal
cis-eQTMs eGenes could be captured through annotation of the eCpG to the
closest gene. eCpGs had less measurement error and were enriched for
active blood regulatory regions and for CpGs reported to be associated
with environmental exposures or phenotypic traits. 40.4% of eQTMs had at
least one genetic variant associated with methylation and expression
levels. The overlap of autosomal cis eQTMs in children’s blood with those
described in adults was small (13.8%), and age-shared cis eQTMs tended to
be proximal to the TSS and enriched for genetic variants.