Genome-wide association studies (GWASs) have identified genetic variants associated with disease, but, as most variants only modestly affect disease risk, the overall medical relevance of GWASs has been questioned. This study explains how a better functional understanding of these variants could be medically useful. The authors found that rs1800693 — a single-nucleotide polymorphism (SNP) in the gene encoding tumour necrosis factor receptor 1 (TNFR1) — leads to the expression of an altered protein (Δ6-TNFR1) that is secreted as a soluble TNF receptor. GWASs previously found that rs1800693 is associated with multiple sclerosis, but not with rheumatoid arthritis, psoriasis or Crohn's disease. Notably, although TNF antagonists can be an effective treatment for these latter diseases, they can exacerbate disease (or even promote disease onset) in patients with multiple sclerosis. This suggests that TNF antagonists mimic the disease-promoting effects of Δ6-TNFR1. Therefore, if combined with proper follow-up studies, GWASs across common autoimmune diseases may help to predict the efficacy of therapies for these diseases.