Analytic P-value calculation for the higher criticism test in finitedproblems.
The higher criticism is effective for testing a joint null hypothesis against a sparse alternative, e.g., for testing the effect of a gene or a genetic pathway that consists ofdgenetic markers. Accurate p-value calculations for the higher criticism based on the asymptotic distribution require a very larged, which is not the case for the number of genetic variants in a gene or a pathway. In this paper we propose an analytic method that accurately computes the p-value of the higher criticism test for finitedproblems. Unlike previous treatments, this method does not rely on asymptotics indor simulation, and is exact for arbitrarydwhen the test statistics are normally distributed. The method is particularly computationally advantageous whendis not large. We illustrate the proposed method with a case-control genome-wide association study of lung cancer and compare its power to competing methods through simulations.
Department of Biostatistics, Harvard University, Boston, Massachusetts 02115, U.S.A.
Ian J
IJ
Barnett
Department of Biostatistics, Harvard University, Boston, Massachusetts 02115, U.S.A.
Xihong
X
Lin
Empirical process; Genome-wide association studies; Higher criticism; Multiple hypothesis testing; Signal detection