1. Re-analysis and meta-analysis of summary statistics from gene–environment interaction studies.
- Author
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Pham, Duy T, Westerman, Kenneth E, Pan, Cong, Chen, Ling, Srinivasan, Shylaja, Isganaitis, Elvira, Vajravelu, Mary Ellen, Bacha, Fida, Chernausek, Steve, Gubitosi-Klug, Rose, Divers, Jasmin, Pihoker, Catherine, Marcovina, Santica M, Manning, Alisa K, and Chen, Han
- Subjects
FIXED effects model ,GENOME-wide association studies ,STATISTICAL models ,STATISTICS ,ACCOUNTING methods ,CONSORTIA - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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