The study by Flannick and collaborators in a nutshell: rare loss-of-function variants in SLC30A8 are overrepresented in unaffected individuals and therefore protect against type 2 diabetes. As these variants are rare (<1%), a cohort of 14,000 individuals is only sufficiently powered to provide suggestive, nominal evidence. Even with 150,000 individuals, the significance level for this association has only barely reached genome-wide significance. The magnitude of this study provides an interesting template for further studies in complex human diseases that try to investigate rare protective or risk factors.