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Multiple endpoints are often naturally clustered based on their scientific interpretations. Tests that compare these clustered outcomes between independent groups may lose efficiency if the cluster structures are not properly accounted for. For the two-sample generalized Behrens-Fisher hypothesis concerning multiple endpoints we propose a cluster-adjusted multivariate test procedure for the comparison and demonstrate its gain in efficiency over test procedures that ignore the clusters. Data from a dietary intervention trial are used to illustrate the methods.

BackgroundThe association studies on human complex traits are admittedly propitious to identify deleterious genetic markers. Compared to single-trait analyses, multiple-trait analyses can arguably make better use of the information on both traits and markers, and thus improve statistical power of association tests prominently. Principal component analysis (PCA) is a well-known useful tool in multivariate analysis and can be applied to this task. Generally, PCA is first performed on all traits and then a certain number of top principal components (PCs) that explain most of the trait variations are selected to construct the test statistics. However, under some situations, only utilizing these top PCs would lead to a loss of important evidences from discarded PCs and thus makes the capability compromised.MethodsTo overcome this drawback while keeping the advantages of using the top PCs, we propose a group accumulated test evidence (GATE) procedure. By dividing the PCs which is sorted in the descending order according to the corresponding eigenvalues into a few groups, GATE integrates the information of traits at the group level.ResultsSimulation studies demonstrate the superiority of the proposed approach over several existing methods in terms of statistical power. Sometimes, the increase of power can reach 25%. These methods are further illustrated using the Heterogeneous Stock Mice data which is collected from a quantitative genome-wide association study.ConclusionsOverall, GATE provides a powerful test for pleiotropic genetic associations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3928-7) contains supplementary material, which is available to authorized users.