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.
Child Neurology Fellow and epilepsy genetics researcher at the Children’s Hospital of Philadelphia (CHOP), USA and Department of Neuropediatrics, Kiel, Germany