"The authors use whole-exome germ line sequencing to analyze whether a set of 27 complement genes is associated with PF. Uncovering much-needed new pathophysiological clues could enable better therapy for patients with PF in the future, but finding new and meaningful connections from a haystack full of molecular possibilities is not trivial.

Using a recently described rarity variant trend test (RVTT) method, the authors assess the combined effect of multiple complement gene variants predicted to result in an altered phenotype. Teasing out the aggregate effect is of importance because the rare variants in question do not have sufficient statistical power to be individually associated with purpurea fulminans."