The ℒ Value: An Estimated Local False Discovery Rate to Replace a p value

2019 ◽  
pp. 81-87
Author(s):  
David R. Bickel
2006 ◽  
Vol 45 (9) ◽  
pp. 1181-1189 ◽  
Author(s):  
D. S. Wilks

Abstract The conventional approach to evaluating the joint statistical significance of multiple hypothesis tests (i.e., “field,” or “global,” significance) in meteorology and climatology is to count the number of individual (or “local”) tests yielding nominally significant results and then to judge the unusualness of this integer value in the context of the distribution of such counts that would occur if all local null hypotheses were true. The sensitivity (i.e., statistical power) of this approach is potentially compromised both by the discrete nature of the test statistic and by the fact that the approach ignores the confidence with which locally significant tests reject their null hypotheses. An alternative global test statistic that has neither of these problems is the minimum p value among all of the local tests. Evaluation of field significance using the minimum local p value as the global test statistic, which is also known as the Walker test, has strong connections to the joint evaluation of multiple tests in a way that controls the “false discovery rate” (FDR, or the expected fraction of local null hypothesis rejections that are incorrect). In particular, using the minimum local p value to evaluate field significance at a level αglobal is nearly equivalent to the slightly more powerful global test based on the FDR criterion. An additional advantage shared by Walker’s test and the FDR approach is that both are robust to spatial dependence within the field of tests. The FDR method not only provides a more broadly applicable and generally more powerful field significance test than the conventional counting procedure but also allows better identification of locations with significant differences, because fewer than αglobal × 100% (on average) of apparently significant local tests will have resulted from local null hypotheses that are true.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Elizabeth Y. Chong ◽  
Yijian Huang ◽  
Hao Wu ◽  
Nima Ghasemzadeh ◽  
Karan Uppal ◽  
...  

2017 ◽  
Author(s):  
Rong W. Zablocki ◽  
Richard A. Levine ◽  
Andrew J. Schork ◽  
Shujing Xu ◽  
Yunpeng Wang ◽  
...  

While genome-wide association studies (GWAS) have discovered thousands of risk loci for heritable disorders, so far even very large meta-analyses have recovered only a fraction of the heritability of most complex traits. Recent work utilizing variance components models has demonstrated that a larger fraction of the heritability of complex phenotypes is captured by the additive effects of SNPs than is evident only in loci surpassing genome-wide significance thresholds, typically set at a Bonferroni-inspired p ≤ 5 x 10-8. Procedures that control false discovery rate can be more powerful, yet these are still under-powered to detect the majority of non-null effects from GWAS. The current work proposes a novel Bayesian semi-parametric two-group mixture model and develops a Markov Chain Monte Carlo (MCMC) algorithm for a covariate-modulated local false discovery rate (cmfdr). The probability of being non-null depends on a set of covariates via a logistic function, and the non-null distribution is approximated as a linear combination of B-spline densities, where the weight of each B-spline density depends on a multinomial function of the covariates. The proposed methods were motivated by work on a large meta-analysis of schizophrenia GWAS performed by the Psychiatric Genetics Consortium (PGC). We show that the new cmfdr model fits the PGC schizophrenia GWAS test statistics well, performing better than our previously proposed parametric gamma model for estimating the non-null density and substantially improving power over usual fdr. Using loci declared significant at cmfdr ≤ 0.20, we perform follow-up pathway analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) homo sapiens pathways database. We demonstrate that the increased yield from the cmfdr model results in an improved ability to test for pathways associated with schizophrenia compared to using those SNPs selected according to usual fdr.


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