Schematic diagram of the CIT. A) Study subjects are sampled for i) a trait of interest, T (for example, cholesterol or fat mass), ii) a potential mediating factor, G (for example, an mRNA or protein concentration), and iii) genotype at a polymorphic locus, L, that is thought to affect both G and T. B) The four component tests of the CIT are conducted yielding four corresponding p-values. (Plots are shown as a conceptual device, see text for details of the actual tests.) Associations in 1 through 3 but not 4 are consistent with causal mediation. C) The largest of the four p-values becomes the omnibus p-value, the final result of the CIT.
Millstein et al. BMC Genetics 2009 10:23 doi:10.1186/1471-2156-10-23