A genomic atlas of systemic interindividual epigenetic variation in humans.

 
TitleA genomic atlas of systemic interindividual epigenetic variation in humans.
Publication TypeJournal Article
Year of Publication2019
AuthorsGunasekara, CJ, C Scott, A, Laritsky, E, Baker, MS, MacKay, H, Duryea, JD, Kessler, NJ, Hellenthal, G, Wood, AC, Hodges, KR, Gandhi, M, Hair, AB, Silver, MJ, Moore, SE, Prentice, AM, Li, Y, Chen, R, Coarfa, C, Waterland, RA
JournalGenome Biol
Volume20
Issue1
Pagination105
Date Published2019 06 03
ISSN1474-760X
KeywordsAged, Brain, Case-Control Studies, Child, Disease, DNA Methylation, Epigenesis, Genetic, Female, Gambia, Genetic Variation, Genome, Human, Humans, Male, Middle Aged, Myocardium, Pregnancy, Prenatal Nutritional Physiological Phenomena, Seasons, Thyroid Gland
Abstract

BACKGROUND: DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific.

RESULTS: For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues.

CONCLUSIONS: In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease.

DOI10.1186/s13059-019-1708-1
Alternate JournalGenome Biol.
PubMed ID31155008
PubMed Central IDPMC6545702
Grant List098386/Z/12/Z / / Wellcome Trust / United Kingdom
MC-A760-5QX00 / / Medical Research Council / United Kingdom
R21 HD087860 / HD / NICHD NIH HHS / United States
S10 OD023469 / OD / NIH HHS / United States
R01 DK111522 / DK / NIDDK NIH HHS / United States
/ / Wellcome Trust / United Kingdom