RT Journal Article
SR Electronic
T1 Reporting correct p-values in VEGAS analyses
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 101014
DO 10.1101/101014
A1 Julian Hecker
A1 Anna Maaser
A1 Dmitry Prokopenko
A1 Heide Loehlein Fier
A1 Christoph Lange
YR 2017
UL http://biorxiv.org/content/early/2017/01/18/101014.abstract
AB 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.