title: Reporting Correct p Values in VEGAS Analyses.
abstract: 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.
authors.affiliation: Institute of Genomic Mathematics,University of Bonn,Bonn,Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Hecker
authors.affiliation: Institute of Human Genetics,University of Bonn,Bonn,Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Maaser
authors.affiliation: Institute of Genomic Mathematics,University of Bonn,Bonn,Germany.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Prokopenko
authors.affiliation: Institute of Genomic Mathematics,University of Bonn,Bonn,Germany.
authors.forename: Heide Loehlein
authors.initials: HL
authors.lastname: Fier
authors.affiliation: Department of Biostatistics,Harvard T.H. Chan School of Public Health,Boston,Massachusetts,USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
mesh_terms: D003627:Data Interpretation, Statistical; D056726:Genetic Association Studies / Q000706:statistics & numerical data*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
keywords: 
                 p values; VEGAS; VEGAS2; gene-based test