Re-analysis and meta-analysis of summary statistics from gene–environment interaction studies

Abstract

Motivation: Summary statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene–environment interactions, there is a need for gene–environment interaction-specific methods that manipulate and use summary statistics. Results: We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene–exposure and/or gene–covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction covariate adjustments. METAGEM (META-analysis of GEM summary statistics) extends current fixed-effects meta-analysis models to incorporate multiple exposures from multiple studies. We demonstrate the value and efficiency of these tools by exploring alternative methods of accounting for ancestry-related population stratification in genome-wide interaction study in the UK Biobank as well as by conducting a multi-exposure genome-wide interaction study meta-analysis in cohorts from the diabetes-focused ProDiGY consortium. These programs help to maximize the value of summary statistics from diverse and complex gene–environment interaction studies. Availability and implementation: REGEM and METAGEM are open-source projects freely available at https://github.com/large-scale-gxe-methods/REGEM and https://github.com/large-scale-gxe-methods/METAGEM.