GEIA

GEIA performs large-scale gene-environment interaction (GEI) analysis to identify genetic variants whose effects are modified by environmental factors in datasets comprising up to millions of samples.

Key Features:

• Scalability: Scales genome-wide GEI analyses to datasets comprising millions of samples.
• Multi-threading Capability: Implements multi-threading to accelerate computation on large datasets.
• Inclusion of Multiple GEI Terms: Supports incorporation of multiple gene-environment interaction terms within analytical models.
• Adjustment for Covariates: Allows adjustment for covariates to control confounding in GEI inference.
• Support for Various Phenotypes: Performs GEI testing for both continuous and binary phenotypes.

Scientific Applications:

• Genetic architecture of complex diseases: Enables identification of genetic variants whose effects are modified by environmental exposures to elucidate genetic architecture of complex diseases.
• Physiological, lifestyle, and treatment interactions: Facilitates investigation of interactions between genetic variants and physiological, lifestyle, or treatment-related exposures.
• Large-scale discovery of interaction loci: Enables detection of novel loci and interaction patterns that may be undetectable in smaller studies.

Methodology:

Validated using rigorous simulation studies to demonstrate scalability to millions of samples; supports joint testing of genetic effects for interaction detection; applied to a gene-sex interaction analysis of waist-hip ratio in the UK Biobank (352,768 unrelated individuals), identifying 39 novel loci.