We have undertaken hypothesis-driven LCA, cross-validated across three large samples: the Early Rheumatoid Arthritis Network (ERAN) cohort and two established RA cohorts from the British Society for Rheumatology Biologics Registers (BSRBR) either commencing tumour necrosis factor (TNF)-α inhibitors or using only non-biologic disease-modifying drugs [23]. The gene discussed is TNF; the disease is rheumatoid arthritis.