Genomic and Epigenomic Signature at the branch-point among Genome, Phenome and Sexome in health and disease: A Multi-Omics approach

Omics sciences have deeply transformed biomedical research. However, this field has largely ignored the effects of sex and gender on genotype–phenotype relationships. The rapid evolution of molecular medicine and genomics led to a new stage of bio-medical research that can now take advantage of new investigative approaches. Progress in genotyping has indeed allowed large-scale genome-wide association studies (GWAS), and this evolution powered the development of functional and integrative multi-omics investigations to address complex diseases. In this context, omics sciences now include transcriptomics, proteomics, metabolomics and microbiomics together with genomics and epigenomics. Of note, the extensive use of these approaches is favoring a closer interaction between preclinical research and clinical setting. In the present chapter, we discuss various multi-layer strategies for omics analyses, including genome-first, phenome-first, and environment-first approaches. Importantly, we emphasize the importance of considering sex, gender, and epigenome, to better understand the determinants of disease development and progression and to improve clinical outcomes.