Despite incredible advances in the recruitment and phenotyping of patients for genomewide association studies (GWAS) in the past decade, the ability to ascertain the causes of complex disease remains a significant challenge. Recent research implies that instead of single variants of large effect, many variants of extremely small effect represent the majority of signal associated with genetic disease. We believe this work is an important step toward increasing the predictive power and interpretability of genetic risk score methods, and that the evolution of such score will help inform and direct research in genetic disease to the benefit of patients and clinicians.