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We approach the problem of combining top-ranking association statistics or P-value from a new perspective which leads to a remarkably simple and powerful method. Statistical methods, such as the Rank Truncated Product (RTP), have been developed for combining top-ranking associations and this general strategy proved to be useful in applications for detecting combined effects of multiple disease components. To increase power, these methods aggregate signals across top ranking SNPs, while adjusting for their total number assessed in a study. Analytic expressions for combined top statistics or P-values tend to be unwieldy, which complicates interpretation, practical implementation, and hinders further developments. Here, we propose the Augmented Rank Truncation (ART) method that retains main characteristics of the RTP but is substantially simpler to implement. ART leads to an efficient form of the adaptive algorithm, an approach where the number of top ranking SNPs is varied to optimize power. We illustrate our methods by strengthening previously reported associations of $mu$-opioid receptor variants with sensitivity to pain.
We review the methods to combine several measurements, in the form of parameter values or $p$-values.
Combining data from several case-control genome-wide association (GWA) studies can yield greater efficiency for detecting associations of disease with single nucleotide polymorphisms (SNPs) than separate analyses of the component studies. We compared
The central aim in this paper is to address variable selection questions in nonlinear and nonparametric regression. Motivated by statistical genetics, where nonlinear interactions are of particular interest, we introduce a novel and interpretable way
Given a family of null hypotheses $H_{1},ldots,H_{s}$, we are interested in the hypothesis $H_{s}^{gamma}$ that at most $gamma-1$ of these null hypotheses are false. Assuming that the corresponding $p$-values are independent, we are investigating com
Many statistical methods have been proposed for variable selection in the past century, but few balance inference and prediction tasks well. Here we report on a novel variable selection approach called Penalized regression with Second-Generation P-Va