DNA methylation, genotype and gene expression: who is driving and who is along for the ride?

Jones, Meaghan J.; Fejes, Anthony P.; Kobor, Michæl S.

doi:10.1186/gb-2013-14-7-126

Cited by 51 publications

(37 citation statements)

References 9 publications

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“…17,21). These overlaps were consistent with our expectation of a relationship between DNA methylation, transcription, and chromatin structure Jones et al 2013). We also tested to what extent our mQTLs may impact organismal-level traits.…”

Section: Applying Our Pooling Approach To Empirical Datasupporting

confidence: 71%

A pooling-based approach to mapping genetic variants associated with DNA methylation

et al. 2015

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DNA methylation is an epigenetic modification that plays a key role in gene regulation. Previous studies have investigated its genetic basis by mapping genetic variants that are associated with DNA methylation at specific sites, but these have been limited to microarrays that cover <2% of the genome and cannot account for allele-specific methylation (ASM). Other studies have performed whole-genome bisulfite sequencing on a few individuals, but these lack statistical power to identify variants associated with DNA methylation. We present a novel approach in which bisulfite-treated DNA from many individuals is sequenced together in a single pool, resulting in a truly genome-wide map of DNA methylation. Compared to methods that do not account for ASM, our approach increases statistical power to detect associations while sharply reducing cost, effort, and experimental variability. As a proof of concept, we generated deep sequencing data from a pool of 60 human cell lines; we evaluated almost twice as many CpGs as the largest microarray studies and identified more than 2000 genetic variants associated with DNA methylation. We found that these variants are highly enriched for associations with chromatin accessibility and CTCF binding but are less likely to be associated with traits indirectly linked to DNA, such as gene expression and disease phenotypes. In summary, our approach allows genome-wide mapping of genetic variants associated with DNA methylation in any tissue of any species, without the need for individual-level genotype or methylation data.

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Section: Applying Our Pooling Approach To Empirical Datasupporting

confidence: 71%

A pooling-based approach to mapping genetic variants associated with DNA methylation

et al. 2015

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“…Across all genes within an individual, the relationship between gene expression and DNA methylation does tend to be negative. When examining a single gene across individuals, however, the relationship can be negative, positive or nonexistent [14,19,20]. Thus, while most genes show the expected – increased DNA methylation results in decreased gene expression – some genes show the opposite pattern, and some show no pattern at all.…”

Section: ’Omics Challengesmentioning

confidence: 99%

The Era of Integrative Genomics: More Data or Better Methods?

Koestler¹,

Jones²,

Kobor³

2014

Epigenomics

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“…These results highlight the complex, tissue-specific relationships among DNA sequence, epigenetic, and gene expression variation that are only beginning to be understood. As the number of positive reports of epigenetic associations with complex disease continues to grow, it will be especially important to identify those associations that cause gene expression changes and those that are only passively linked to such changes, in order to more precisely define true biomarkers of disease and/or possible targets for pharmaceutical interventions [81].…”

Section: Defining Mechanistic Relationships Among Dna Sequence Epigementioning

confidence: 99%

Epigenetic Epidemiology of Psychiatric Disorders

Uddin

Bustamante

Toyokawa

2014

Epigenetics in Psychiatry

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DNA methylation, genotype and gene expression: who is driving and who is along for the ride?

Abstract: A new study integrates genome-wide SNP genotyping, RNA-Seq and DNA methylation in human cells, revealing their relationships and posing new questions about causality.

Cited by 51 publications

References 9 publications

A pooling-based approach to mapping genetic variants associated with DNA methylation

A pooling-based approach to mapping genetic variants associated with DNA methylation

The Era of Integrative Genomics: More Data or Better Methods?

Epigenetic Epidemiology of Psychiatric Disorders

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