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- Title
Incorporating genome-wide methylation and genotype data to elucidate how region-wise methylation level might influence allele-defined relative risks.
- Authors
Romanowska, Julia; Haaland, Øystein A.; Gjerdevik, Miriam; Jonassen, Inge; Lie, Rolv T.; Jugessur, Astanand; Gjessing, Håkon K.
- Abstract
Introduction: The genetic code is tightly linked to epigenetic instructions as to which genes to express, when and where. The most studied epigenetic mark is DNA methylation at CpG dinucleotides. Today's technology enables a rapid assessment of DNA sequence and methylation levels at a singlesite resolution for hundreds of thousands of sites in the human genome, in thousands of individuals at a time. This enormous wealth of data calls for new statistical approaches that can harness their full potential. Aims: To integrate the DNA methylation data and genetic association analyses. Methods: We propose a new method that treats the level of DNA methylation as an environmental exposure. We developed two new approaches to search for statistical interactions between a given SNP and DNA methylation (GxM), and between a parent-of-origin effect and DNA methylation (PoOxM). The new methods and approaches were implemented in the R package Haplin (https://people.uib.no/gjessing/genetics/software/haplin/). Results: We tested the methods on genotype data from mother-father-child triads and DNA methylation data from the children only. The phenotype of choice was orofacial clefts (OFC). Our results show that identifying these interactive effects are dependent on the genomic region in which the CpGs reside and on the number of methylation level strata. Conclusions: We found that including the methylation level around the SNP can significantly deacrease or increase the relative risk of the OFC. We discuss also that in such an analysis it is important to include control data.
- Subjects
EPIGENETICS; DNA methylation; GENETIC code; NUCLEOTIDE sequence; ALLELES
- Publication
Norsk Epidemiologi, 2018, Vol 28, Issue Supplement 1, p42
- ISSN
0803-2491
- Publication type
Article