Genes governing nucleic acid metabolism and sensing provide a mechanistic bridge to interferon biology: rare and common variants in TLR7, IFIH1 (MDA5), TREX1, ADAR1, DNASE1L3, RNASEH2, and TMEM173 (STING1) potentiate accumulation or recognition of self-derived nucleic acids, lowering the threshold for type I interferon (IFN) production and imprinting an “IFN-high” endotype in subsets of SLE, dermatomyositis, and related conditions [4,5,6,7]. Here, IFIH1 is linked to systemic lupus erythematosus.