Mapping Allele-Specific DNA Methylation: A New Tool for Maximizing Information from GWAS
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In this issue of The Journal, an article by Schalkwyk et al.(1) shows the landscape of allele-specific DNA methylation (ASM) in the human genome. ASM has long been studied as a hallmark of imprinted genes, and a chromosome-wide version of this phenomenon occurs, in a random fashion, during X chromosome inactivation in female cells. But the type of ASM motivating the study by Schalkwyk et al. is different. They used a high-resolution, methylation-sensitive SNP array (MSNP) method for genome-wide profiling of ASM in total peripheral-blood leukocytes (PBL) and buccal cells from a series of monozygotic twin pairs. Their data bring a new level of detail to our knowledge of a newly recognized phenomenon-nonimprinted, sequence-dependent ASM. They document the widespread occurrence of this phenomenon among human genes and discuss its basic implications for gene regulation and genetic-epigenetic interactions. But this paper and recent work from other laboratories(2,3) raises the possibility of a more immediate and practical application for ASM mapping, namely to help extract maximum information from genome-wide association studies.
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Many genetic and epigenetic factors, including multiple rare single nucleotide variants, copy number variations, and other structural variation, likely contribute to common complex diseases.
“It is now widely believed that many genetic and epigenetic factors are likely to contribute to common complex diseases, including multiple rare SNVs (defined by convention as those that have frequencies < 1%), copy number variations (CNVs), and other forms of structural variation. 3–12”
From Statistical analysis strategies for association studies involving rare variants (2010) · cites this paper as [5]
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Statistical analysis strategies for association studies involving rare variants
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- Authors
- Tycko, B.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Tycko, Benjamin
- ORCID
- Tycko, Benjamin
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 86
- Issue
- 2
- Pages
- 109-112
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2820186
- OpenAlex
- W2041936754
- Cited by
- 39
- References
- 38
- Citations by year
- 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 1 · 2012: 4
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- allele-specific methylation, genome-wide association study, epigenetic inheritance, genetic-epigenetic interaction, monozygotic twins, gene expression regulation, imprinted genes, X chromosome inactivation
- MeSH terms
- Alleles, Animals, Base Sequence, Chromosome Mapping, Humans, DNA Methylation, Polymorphism, Single Nucleotide, Epigenesis, Genetic, Mice, Genome-Wide Association Study
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