For almost a decade, equipped with powerful technologies for large-scale genotyping and sequencing analyses, geneticists around the world have embarked on an unprecedented and collaborative effort to systematically interrogate the full spectrum of common, low frequency and rare variation that contributes to human health and diseases. Such effort has already led to the discovery of thousands of human health or disease-associated genetic variants, and much more are expected to be uncovered through even broader international consortia. While these promising discoveries have already advanced our understanding on disease development, concrete progress is yet to be made regarding to the causal understanding of pathogenesis and mechanisms of diseases. While there are intensified efforts to functionally annotate these genetic variants through the integration of epigenomic information, the emergence and marriage of in vitro ESCs or iPSCs-based human tissue engineering technologies and new powerful tools for large-scale genomic editing/mutagenesis have offered new opportunities for human disease modeling and deep biological understanding of diseases, promising the identification of drug targets and biomarkers for improving clinical practice and public health. This Natureconference, co-organized by Nature Genetics, Central South University and Anhui Medical University of China will discuss the new progress in the genetic and genomic analysis of diseases and explore the challenges as well as opportunities for moving beyond into disease biology and clinical application.