With the latest advancements in genomic science, the approach of metagenomics that enables to study microorganisms without any need of culturing and isolation has evolved. In the light of these technical achievements the role of the human microbiome in health and disease states has started to be revealed, redefining human being as a ‘superorganism'. Accordingly, human microbiome is subject to significant changes in disease state called dysbiosis. On the other hand, it was reported a short while ago that some genetic variations in human genome are associated with the microbial components of human microbiome and the presence/absence or relative abundance of taxonomic units in it. When all of these findings are gathered, it can be observed that an important portion of the genetic variations associated with diseases (e.g. diabetes, arthritis) are also overlapped with related microbiomic variations. A novel factor, microbiome, is expected to weigh in the relationship of the disease and the host genetics in the near future. Therefore novel experimental designs encompassing metagenomic, and other omic analyses of human genomehuman microbiome, as well as other omics, in the context of disease will be needed. Human genome-human microbiome relationship is presumably both epistatic and pleiotropic. For that reason, it is inevitable that the future genomic projections should employ Metagenome-Wide Association Studies (MGWAS) bioinformatics considering the multi-genic effects of genetic variations and the microbiome analysis.