Open AccessCo-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms
Author(s) -
Brandon L. Pierce,
Tong Lin,
Maria Argos,
Kathryn Demanelis,
Farzana Jasmine,
Muhammad Rakibuz-Zaman,
Golam Sarwar,
Tariqul Islam,
Hasan Shahriar,
Mahfuzar Rahman,
Muhammad Yunus,
Muhammad G. Kibriya,
Lin S. Chen,
Habibul Ahsan
Publication year - 2018
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/s41467-018-03209-9
Subject(s) - expression quantitative trait loci , dna methylation , genetics , biology , methylation , quantitative trait locus , single nucleotide polymorphism , gene , computational biology , gene expression , genotype
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.