Genome-wide association studies (GWASs) have generally focused on susceptibility to disease, whereas the genetics of complex-disease progression and outcome has received little attention. Here, the authors use data from previous GWASs to identify a single-nucleotide polymorphism (SNP) in the forkhead box O3 gene (FOXO3) that is associated with the severity of, but not the susceptibility to, Crohn's disease, rheumatoid arthritis and malaria infection. This finding shows how new biological insights can be gained from re-analyses of GWAS data and has implications for predicting disease outcome and developing new therapies.