Lange, C. | bioRxiv Science

bioRxiv2017

An almost nearly optimal sequential testing approach to permutation-based association testing

The following technical report describes the technical details for the implementation of a sequential testing approach to permutation-based association testing in whole-genome sequencing studies. The sequential testing approach enables to control the probability of a type 1 and type 2 error at arbitrary small pre-specified levels and approaches the theoretical minimum of expected number of required permutations as these levels go to zero.

genetics↗

bioRxiv2017

Reporting correct p-values in VEGAS analyses

VEGAS (versatile gene-based association study) is a popular methodological framework to perform gene-based tests based on summary statistics from single-variant analyses. The approach incorporates linkage disequilibrium information from reference panels to account for the correlation of test statistics. The gene-based test can utilize three different types of tests. In 2015, the improved framework VEGAS2, using more detailed reference panels, was published. Both versions provide user-friendly web- and offline-based tools for the analysis. However, the implementation of the popular top-percentage test is erroneous in both versions. The p-values provided by VEGAS2 are deflated/anti-conservative. Based on real data examples, we demonstrate that this can increase substantially the rate of false positive findings and can lead to inconsistencies between different test options. We also provide code that allows the user of VEGAS to compute correct p-values.

genetics↗