GEM (Gene-Environment interaction analysis in Millions of samples) open-source software written in C++ provides scalable and flexible large-scale Genetic Wide Association Analysis (GWAS) through multi-threading paradigms. Traditional bio-statistical methods and computations to tackle the inter-relations of gene and diseases cost significant computation burden, e.g., inverting the genetic relation matrix (GRM). GEM optimizes the execution time and memory usage, facilitating the next generation of large-scale GWAS. Thus GEM enables important discoveries for genetic understanding and personalized medicine.

---