Gene-methylation interactions: discovering region-wise DNA methylation levels that modify SNP-associated disease risk.

Clinical Epigenetics
Julia RomanowskaHåkon K. Gjessing

Abstract

Current technology allows rapid assessment of DNA sequences and methylation levels at a single-site resolution for hundreds of thousands of sites in the human genome, in thousands of individuals simultaneously. This has led to an increase in epigenome-wide association studies (EWAS) of complex traits, particularly those that are poorly explained by previous genome-wide association studies (GWAS). However, the genome and epigenome are intertwined, e.g., DNA methylation is known to affect gene expression through, for example, genomic imprinting. There is thus a need to go beyond single-omics data analyses and develop interaction models that allow a meaningful combination of information from EWAS and GWAS. We present two new methods for genetic association analyses that treat offspring DNA methylation levels as environmental exposure. Our approach searches for statistical interactions between SNP alleles and DNA methylation (G ×Me) and between parent-of-origin effects and DNA methylation (PoO ×Me), using case-parent triads or dyads. We use summarized methylation levels over nearby genomic region to ease biological interpretation. The methods were tested on a dataset of parent-offspring dyads, with EWAS data on the offspring. Our r...Continue Reading

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Methods Mentioned

BETA
chip

Software Mentioned

Haplin
ensembl browser
QuickGO
ggrepel
Bitbucket
R package biomaRt
R
PoO
R package Haplin
×Me

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