In this large prospective study conducted in three independent cohorts, we observed no substantial interaction between obesity and the NFKB1 - 94ins/delATTG promoter polymorphism in relation to the risk of incident ACS; however, joint exposure to general or abdominal obesity and the variant allele was associated with the highest risk of ACS. The gene discussed is NFKB1; the disease is obesity due to melanocortin 4 receptor deficiency.