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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Multiple testing in disease mapping and descriptive epidemiology
Dolores Catelan1, Annibale Biggeri
1Department of Statistics G. Parenti, University of Florence, Viale Morgagni 59, Florence, Italy. catelan@ds.unifi.it
Abstract:
The problem of multiple testing is rarely addressed in disease mapping or descriptive epidemiology. This issue is relevant when a large number of small areas or diseases are analysed. Control of the family wise error rate (FWER), for example via the Bonferroni correction, is avoided because it leads to loss of statistical power. To overcome such difficulties, control of the false discovery rate (FDR), the expected proportion of false rejections among all rejected hypotheses, was proposed in the context of clinical trials and genomic data analysis. FDR has a Bayesian interpretation and it is the basis of the so called q-value, the Bayesian counterpart of the p-value. In the present work, we address the multiplicity problem in disease mapping and show the performance of the FDR approach with two real examples and a small simulation study. The examples consider testing multiple diseases for a given area or multiple areas for a given disease. Using unadjusted p-values for multiple testing, an inappropriately large number of areas or diseases at altered risk are identified, whilst FDR procedures are appropriate and more powerful than the control of the FWER with the Bonferroni correction. We conclude that the FDR approach is adequate to screen for high/low risk areas or for disease excess/deficit and useful as a complementary procedure to point estimates and confidence intervals.
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