Multi-trait analysis of gene-by-environment interactions in large-scale genetic studies.

The article focuses on MTAGEI (Multi-Trait Analysis of Gene–Environment Interactions), a novel, computationally efficient framework designed to improve the detection of genotype-by-environment interactions (GEI) across multiple traits using summary statistics. MTAGEI enhances statistical power by aggregating GEI signals over multiple traits and genetic variants, accommodating diverse genetic architectures through an omnibus testing approach that combines single- and multi-trait as well as single- and multi-variant analyses. Extensive simulations demonstrate that MTAGEI controls type I error and outperforms existing single-trait GEI methods in power, while application to UK Biobank whole exome sequencing data identifies additional lipid-associated genes and a significant APOE gene-by-sex interaction missed by other methods. MTAGEI facilitates large-scale consortium-based meta-analyses by enabling privacy-preserving summary statistic sharing and is implemented in an R package available on GitHub.