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

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

Author information

1
Department of Public Health Sciences, The University of Chicago, Chicago, IL, 60637, USA. brandonpierce@uchicago.edu.
2
Department of Human Genetics, The University of Chicago, Chicago, IL, 60637, USA. brandonpierce@uchicago.edu.
3
Comprehensive Cancer Center, The University of Chicago, Chicago, IL, 60637, USA. brandonpierce@uchicago.edu.
4
Department of Public Health Sciences, The University of Chicago, Chicago, IL, 60637, USA.
5
Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, IL, 60612, USA.
6
UChicago Research Bangladesh, Mohakhali, Dhaka, 1230, Bangladesh.
7
Research and Evaluation Division, BRAC, Dhaka, 1212, Bangladesh.
8
International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, 1000, Bangladesh.
9
Department of Public Health Sciences, The University of Chicago, Chicago, IL, 60637, USA. habib@uchicago.edu.
10
Department of Human Genetics, The University of Chicago, Chicago, IL, 60637, USA. habib@uchicago.edu.
11
Comprehensive Cancer Center, The University of Chicago, Chicago, IL, 60637, USA. habib@uchicago.edu.
12
Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA. habib@uchicago.edu.

Abstract

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.

PMID:
29476079
PMCID:
PMC5824840
DOI:
10.1038/s41467-018-03209-9
[Indexed for MEDLINE]
Free PMC Article

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