Co-occurring eQTLs and mQTLs: detecting shared causal variants and shared biological mechanisms

Pierce, B.; Tong, L.; Argos, M.; Jasmine, F.; Rakibuz-Zaman, M.; Sarwar, G.; Islam, M. T.; Shahriar, H.; Islam, T.; Rahman, M.; Yunus, M.; Kibriya, M. G.; Chen, L. S.; Ahsan, H.

doi:10.1101/094656

bioRxiv · 10.1101/094656

Co-occurring eQTLs and mQTLs: detecting shared causal variants and shared biological mechanisms

Pierce, B.·Tong, L.·Argos, M.·Jasmine, F.·Rakibuz-Zaman, M.·Sarwar, G.·Islam, M. T.·Shahriar, H.·Islam, T.·Rahman, M.·Yunus, M.·Kibriya, M. G.·Chen, L. S.·Ahsan, H.

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Abstract

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.

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Pierce, B., Tong, L., Argos, M., Jasmine, F., Rakibuz-Zaman, M., Sarwar, G., Islam, M. T., Shahriar, H., Islam, T., Rahman, M., Yunus, M., Kibriya, M. G., Chen, L. S., Ahsan, H.. 2016-12-15. Co-occurring eQTLs and mQTLs: detecting shared causal variants and shared biological mechanisms. https://doi.org/10.1101/094656

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