Epigenetic alterations consisting mainly of DNA methylation alterations and histone modification alterations are frequently observed in cancers associated with chronic inflammation and/or persistent infection with viruses or other pathogenic microorganisms, or with cigarette smoking. Accumulating evidence suggests that alterations of DNA methylation are involved even in the early and precancerous stages. On the other hand, in patients with cancers, aberrant DNA methylation is frequently associated with tumor aggressiveness and poor patient outcome. Recently, epigenome alterations have been attracting a great deal of attention from researchers who are focusing on not only cancers but also neuronal, immune and metabolic disorders. In order to accurately identify disease-specific epigenome profiles that could be potentially applicable for disease prevention, diagnosis and therapy, strict comparison with standard epigenome profiles of normal tissues is indispensable. However, epigenome mechanisms show heterogeneity among tissues and cell lineages. Therefore, it is not easy to obtain a comprehensive picture of standard epigenome profiles of normal tissues. In 2010, the International Human Epigenome Consortium (IHEC) was established to coordinate the production of reference maps of human epigenomes for key cellular states. In order to gain substantial coverage of the human epigenome, the IHEC has set an ambitious goal to decipher at least 1000 epigenomes within the next 7-10 years. We consider that pathway analysis using genes showing multilayer-omics abnormalities, including genome, epigenome, transcriptome, proteome and metabolome abnormalities, may be useful for elucidating the molecular background of pathogenesis and for exploring possible therapeutic targets for each disease.