The article discusses the development and challenges of Epigenome-Wide Association Studies (EWAS) in the context of common human diseases. EWAS aim to identify epigenetic variations, particularly DNA methylation (DNAm), that are associated with disease. The authors highlight the importance of integrating EWAS with Genome-Wide Association Studies (GWAS) to better understand the complex interplay between genetic and epigenetic factors in disease etiology. They address key considerations for EWAS design, including sample selection, statistical significance, power, confounding factors, and follow-up studies. The article also explores the types of epigenetic information, the role of epigenetic variation in health and disease, and the potential for EWAS to identify disease-risk and drug-response epigenetic markers. Additionally, it discusses the integration of EWAS and GWAS data to uncover genetic predispositions that function through epigenetic mechanisms. The authors emphasize the need for large-scale, well-powered EWAS and the development of appropriate resources and tools to advance the field.The article discusses the development and challenges of Epigenome-Wide Association Studies (EWAS) in the context of common human diseases. EWAS aim to identify epigenetic variations, particularly DNA methylation (DNAm), that are associated with disease. The authors highlight the importance of integrating EWAS with Genome-Wide Association Studies (GWAS) to better understand the complex interplay between genetic and epigenetic factors in disease etiology. They address key considerations for EWAS design, including sample selection, statistical significance, power, confounding factors, and follow-up studies. The article also explores the types of epigenetic information, the role of epigenetic variation in health and disease, and the potential for EWAS to identify disease-risk and drug-response epigenetic markers. Additionally, it discusses the integration of EWAS and GWAS data to uncover genetic predispositions that function through epigenetic mechanisms. The authors emphasize the need for large-scale, well-powered EWAS and the development of appropriate resources and tools to advance the field.