RT Journal Article
SR Electronic
T1 Co-occurring eQTLs and mQTLs: detecting shared causal variants and shared biological mechanisms
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 094656
DO 10.1101/094656
A1 Brandon L. Pierce
A1 Lin Tong
A1 Maria Argos
A1 Farzana Jasmine
A1 Muhammad Rakibuz-Zaman
A1 Golam Sarwar
A1 Md. Tariqul Islam
A1 Hasan Shahriar
A1 Tariqul Islam
A1 Mahfuzar Rahman
A1 Md. Yunus
A1 Muhammad G. Kibriya
A1 Lin S. Chen
A1 Habibul Ahsan
YR 2016
UL http://biorxiv.org/content/early/2016/12/15/094656.abstract
AB Inherited genetic variation impacts local gene expression and DNA methylation in humans. Expression and methylation quantitative trait loci (cis-eQTLs and cis-mQTLs) often occur at the same genomic location, suggesting a common causal variant and shared mechanism. Using DNA and RNA from peripheral blood of Bangladeshi individuals, we use “co-localization” methods to identify 3,695 eQTL-mQTL pairs that are likely to share a causal variant. Using partial correlation analysis and mediation analysis, we identify >500 pairs with evidence of a causal relationships between expression and methylation (i.e., shared mechanism) with many additional pairs that we are underpowered to detect. These co-localized pairs are enriched for SNPs showing opposite effects on expression and methylation, although a many affect multiple CpGs in opposite directions. Evidence of shared SNP-age interaction also supports shared mechanisms for two eQTL-mQTL pairs. This work demonstrates the pervasiveness of co-regulated expression and methylation traits in the human genome. This approach can be applied to other types of molecular QTLs to enhance our understanding of regulatory mechanisms.