Epigenome-wide association studies: current knowledge, strategies and recommendations

Clinical Epigenetics

Vicky Maltby¹  Alexandre Xavier¹  Rodney J. Scott²  Maria Pia Campagna³  Helmut Butzkueven⁴  Vilija G. Jokubaitis⁴  Rodney A. Lea⁵  Jeannette Lechner-Scott⁶ 

[1] Centre for Information Based Medicine, Hunter Medical Research Institute, Newcastle, Australia;School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia;Centre for Information Based Medicine, Hunter Medical Research Institute, Newcastle, Australia;School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia;Division of Molecular Medicine, New South Wales Health Pathology North, Newcastle, Australia;Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia;Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia;Department of Neurology, Alfred Health, Melbourne, Australia;School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia;Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia;School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia;Department of Neurology, Division of Medicine, John Hunter Hospital, Newcastle, Australia;

关键词: Epigenetics;    Methylation;    EWAS;    ChAMP;    Complex diseases;    Bioinformatics;   

DOI  :  10.1186/s13148-021-01200-8

来源: Springer

【 摘 要 】

The aetiology and pathophysiology of complex diseases are driven by the interaction between genetic and environmental factors. The variability in risk and outcomes in these diseases are incompletely explained by genetics or environmental risk factors individually. Therefore, researchers are now exploring the epigenome, a biological interface at which genetics and the environment can interact. There is a growing body of evidence supporting the role of epigenetic mechanisms in complex disease pathophysiology. Epigenome-wide association studies (EWASes) investigate the association between a phenotype and epigenetic variants, most commonly DNA methylation. The decreasing cost of measuring epigenome-wide methylation and the increasing accessibility of bioinformatic pipelines have contributed to the rise in EWASes published in recent years. Here, we review the current literature on these EWASes and provide further recommendations and strategies for successfully conducting them. We have constrained our review to studies using methylation data as this is the most studied epigenetic mechanism; microarray-based data as whole-genome bisulphite sequencing remains prohibitively expensive for most laboratories; and blood-based studies due to the non-invasiveness of peripheral blood collection and availability of archived DNA, as well as the accessibility of publicly available blood-cell-based methylation data. Further, we address multiple novel areas of EWAS analysis that have not been covered in previous reviews: (1) longitudinal study designs, (2) the chip analysis methylation pipeline (ChAMP), (3) differentially methylated region (DMR) identification paradigms, (4) methylation quantitative trait loci (methQTL) analysis, (5) methylation age analysis and (6) identifying cell-specific differential methylation from mixed cell data using statistical deconvolution.

【 授权许可】

CC BY