Modeling dependency structures in 450k DNA methylation data

Haakon E. Nustad*, Ingelin Steinsland, Miina Ollikainen, Emma Cazaly, Jaakko Kaprio, Yuval Benjamini, Kristina Gervin, Robert Lyle*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Motivation: DNA methylation has been shown to be spatially dependent across chromosomes. Previous studies have focused on the influence of genomic context on the dependency structure, while not considering differences in dependency structure between individuals. Results: We modeled spatial dependency with a flexible framework to quantify the dependency structure, focusing on inter-individual differences by exploring the association between dependency parameters and technical and biological variables. The model was applied to a subset of the Finnish Twin Cohort study (N 1611 individuals). The estimates of the dependency parameters varied considerably across individuals, but were generally consistent across chromosomes within individuals. The variation in dependency parameters was associated with bisulfite conversion plate, zygosity, sex and age. The age differences presumably reflect accumulated environmental exposures and/or accumulated small methylation differences caused by stochastic mitotic events, establishing recognizable, individual patterns more strongly seen in older individuals.

Original languageAmerican English
Pages (from-to)885-891
Number of pages7
JournalBioinformatics
Volume38
Issue number4
DOIs
StatePublished - 15 Feb 2022

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