Self-contained gene-set analysis tests whether the genes in a gene-set are jointly associated with the phenotype of interest. As such, using this variable Z a very simple intercept-only linear regression model can now be formulated for each gene set s of the formZs=β01→+εs, where Z s is the subvector of Z corresponding to the genes in s. Evaluating β 0 = 0 against the alternative β 0 > 0 yields a self-contained test, since under the self-contained null hypothesis that none of the genes is associated with the phenotype z g has a standard normal distribution for every gene g.
