title: Tissue-specific patterns of allelically-skewed DNA methylation.
abstract: While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood.
authors.affiliation: a Institute of Psychiatry, Psychology and Neuroscience, King's College London , London , UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Marzi
authors.affiliation: b Department of Psychological Sciences , Birkbeck, University of London , London , UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Meaburn
authors.affiliation: c University of Exeter Medical School, University of Exeter , Exeter , UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Dempster
authors.affiliation: c University of Exeter Medical School, University of Exeter , Exeter , UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Lunnon
authors.affiliation: a Institute of Psychiatry, Psychology and Neuroscience, King's College London , London , UK.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Paya-Cano
authors.affiliation: c University of Exeter Medical School, University of Exeter , Exeter , UK.
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Smith
authors.affiliation: a Institute of Psychiatry, Psychology and Neuroscience, King's College London , London , UK.
authors.forename: Manuela
authors.initials: M
authors.lastname: Volta
authors.affiliation: a Institute of Psychiatry, Psychology and Neuroscience, King's College London , London , UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Troakes
authors.affiliation: d School of Biological Sciences, University of Essex , Colchester , UK.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Schalkwyk
authors.affiliation: a Institute of Psychiatry, Psychology and Neuroscience, King's College London , London , UK.|c University of Exeter Medical School, University of Exeter , Exeter , UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
mesh_terms: D000483:Alleles; D001921:Brain / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
keywords: Allele-specific DNA methylation; SNP; blood; brain; cerebellum; cortex; epigenetics; genomic imprinting