Identification of blood autosomal cis-expression quantitative trait methylation (cis-eQTMs) in children

Publication Summary

Background The identification of expression quantitative trait methylation (eQTMs), defined as correlations between gene expression and DNA methylation levels, might help the biological interpretation of epigenome-wide association studies (EWAS). We aimed to identify autosomal cis-eQTMs in child 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 (transcription start site (TSS) within a window of 1 Mb) was assessed by fitting 13.6 M linear regressions adjusting for sex, age, and cohort. Results We identified 63,831 autosomal cis-eQTMs, representing 35,228 unique CpGs and 11,071 unique transcript clusters (TCs, genes). 74.3% of these cis-eQTMs were located at <250 kb, 60.0% showed an inverse relationship and 23.9% had at least one genetic variant associated with the methylation and expression levels. They were enriched for active blood regulatory regions. Adjusting for cellular composition decreased the number of cis-eQTMs to 37.7%, suggesting that some of them were cell type-specific. The overlap of child blood cis-eQTMs with those described in adults was small, and child and adult shared cis-eQTMs tended to be proximal to the TSS, enriched for genetic variants and with lower cell type specificity. Only half of the cis-eQTMs could be captured through annotation to the closest gene. Conclusions This catalogue of blood autosomal cis-eQTMs in children can help the biological interpretation of EWAS findings, and is publicly available at https://helixomics.isglobal.org/.