Co-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms

Nat Commun. 2018 Feb 23;9(1):804. doi: 10.1038/s41467-018-03209-9.


Inherited genetic variation affects local gene expression and DNA methylation in humans. Most expression quantitative trait loci (cis-eQTLs) occur at the same genomic location as a methylation QTL (cis-meQTL), suggesting a common causal variant and shared mechanism. Using DNA and RNA from peripheral blood of Bangladeshi individuals, here we use co-localization methods to identify eQTL-meQTL pairs likely to share a causal variant. We use partial correlation and mediation analyses to identify >400 of these pairs showing evidence of a causal relationship between expression and methylation (i.e., shared mechanism) with many additional pairs we are underpowered to detect. These co-localized pairs are enriched for SNPs showing opposite associations with expression and methylation, although many SNPs affect multiple CpGs in opposite directions. This work demonstrates the pervasiveness of co-regulated expression and methylation in the human genome. Applying this approach to other types of molecular QTLs can enhance our understanding of regulatory mechanisms.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Bangladesh
  • DNA Methylation*
  • Female
  • Gene Expression
  • Genetic Variation*
  • Genome, Human
  • Genome-Wide Association Study
  • Genomics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Young Adult