Here we have described our PRSice software, illustrating its use with three PRS studies. We have illustrated the potential benefit of obtaining the best-fit PRS and have estimated a corresponding significance threshold. There is great potential for the future application of PRS in genetics: for gaining insights into the genetic architecture of a trait by comparing observed PRS with theoretical expectations across a range of PT (International Schizophrenia Consortium, 2009), for assessing the genetic overlap of a trait(s) across populations, for use as biomarkers, as instrumental variables, or even to provide evolutionary insights (Berg and Coop, 2014). The PRS approach, and PRSice software, could be extended to test the effects of copy number variants, epigenetic markers and more. We believe that PRSice can simplify PRS studies greatly, expand the application of PRS and aid the implementation of best-practice in PRS studies.