Individuals with renal involvement exhibit more robust hypomethylation both globally and specifically within interferon-regulated genes compared to those without renal involvement▪The type I interferon master regulator gene IRF7 is only hypomethylated in those with lupus nephritisHypomethylation within CHST12 is 86% sensitive and 64% specific for lupus nephritis (23). Here, IRF7 is linked to lupus nephritis.