Ten Years of EWAS

Abstract

Epigenome-wide association study (EWAS) has been applied to analyze DNA methylation variation in complex diseases for a decade, and epigenome as a research target has gradually become a hot topic of current studies. The DNA methylation microarrays, next-generation, and third-generation sequencing technologies have prepared a high-quality platform for EWAS. Here, the progress of EWAS research is reviewed, its contributions to clinical applications, and mainly describe the achievements of four typical diseases. Finally, the challenges encountered by EWAS and make bold predictions for its future development are presented.

EWAS Open Platform: integrated data, knowledge and toolkit for epigenome-wide association study

“…With the explosive growth of epigenome-wide association studies (EWAS), huge amounts of data and knowledge related to EWAS have been accumulated ( 1 ). Since these data hold great potential for clinical translations, a standardized platform for data archive, retrieval and exploration is indispensable.…”

Systemic interindividual epigenetic variation in humans is associated with transposable elements and under strong genetic control

“…For over ten years the Illumina methylation platform has been the predominant tool for population studies of DNA methylation (22, 30). A major reason is that it interrogates a stable subset of CpG sites within the human genome (yielding one quantitative value for each), simplifying data sharing and integration across multiple studies and populations.…”

“…Lastly, whereas our current data on CoRSIV mQTL is based on a mostly Caucasian cohort in the US, it is possible that additional sources of variation (for example, due to periconceptional environment (37,59,60)) will be uncovered as CoRSIVs are studied in a broader range of ethnic and cultural contexts, providing insights into gene by environment interactions. For over ten years the Illumina methylation platform has been the predominant tool for population studies of DNA methylation (22,30). A major reason is that it interrogates a stable subset of CpG sites within the human genome (yielding one quantitative value for each), simplifying data sharing and integration across multiple studies and populations.…”

“…Several large consortium projects, including the Roadmap Epigenome Project (27), the Blueprint Epigenome Project (28), and the International Human Epigenome Consortium (29), focused primarily on characterizing tissue- and cell type-specific epigenetic variation rather than mapping out human genomic regions of interindividual epigenetic variation. The EWAS field therefore relied almost exclusively on Illumina arrays (30) which were designed without consideration of interindividual variation in DNA methylation (31, 32) and generally target CpGs that show little (33–36). To address this lacuna, we recently conducted an unbiased screen for correlated regions of systemic (i.e.…”

Epigenetics provides a bridge between early nutrition and long‐term health and a target for disease prevention

“…In particular, variations in DNA methylation have been extensively studied. 16 Perinatal nutritional status has been associated with permanent changes in IGF2 methylation following maternal exposure to a nutritional challenge. In a Dutch cohort, children who were prenatally exposed to wartime famine in 1944–1945, exhibited lower DNA methylation of IGF2 , which is a modulator of a newborn's foetal growth and development.…”