Dependency and truncated forms of combinations in multivariate combination-based permutation tests and ordered categorical variables

Quite an important problem usually occurs in several multi-dimensional hypotheses testing problems when variables are correlated. In this framework the non-parametric combination (NPC) of a finite number of dependent permutation tests is suitable to cover almost all real situations of practical interest since the dependence relations among partial tests are implicitly captured by the combining procedure itself without the need to specify them [Pesarin F, Salmaso L. Permutation tests for complex data: theory, applications and software. Chichester: Wiley; 2010a]. An open problem related to NPC-based tests is the impact of the dependency structure on combined tests, especially in the presence of categorical variables. This paper’s goal is firstly to investigate the impact of the dependency structure on the possible significance of combined tests in cases of ordered categorical responses using Monte Carlo simulations, then to propose some specific procedures aimed at improving the power of multivariate combination-based permutation tests. The results show that an increasing level of correlation/association among responses negatively affects the power of combination-based multivariate permutation tests. The application of special forms of combination functions based on the truncated product method [Zaykin DV, Zhivotovsky LA, Westfall PH, Weir BS. Truncated product method for combining p-values. Genet Epidemiol. 2002;22:170–185; Dudbridge F, Koeleman BPC. Rank truncated product of p-values, with application to genomewide association scans. Genet Epidemiol. 2003;25:360–366] or on Liptak combination allowed us, using Monte Carlo simulations, to demonstrate the possibility of mitigating the negative effect on power of combination-based multivariate permutation tests produced by an increasing level of correlation/association among responses.