Smooth-threshold multivariate genetic prediction incorporating gene–environment interactions

for Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticlepeer-review


We propose a genetic prediction modeling approach for genome-wide association study (GWAS) data that can include not only marginal gene effects but also gene–environment (GxE) interaction effects—i.e., multiplicative effects of environmental factors with genes rather than merely additive effects of each. The proposed approach is a straightforward extension of our previous multiple regression-based method, STMGP (smooth-threshold multivariate genetic prediction), with the new feature being that genome-wide test statistics from a GxE interaction analysis are used to weight the corresponding variants. We develop a simple univariate regression approximation to the GxE interaction effect that allows a direct fit of the STMGP framework without modification. The sparse nature of our model automatically removes irrelevant predictors (including variants and GxE combinations), and the model is able to simultaneously incorporate multiple environmental variables. Simulation studies to evaluate the proposed method in comparison with other modeling approaches demonstrate its superior performance under the presence of GxE interaction effects. We illustrate the usefulness of our prediction model through application to real GWAS data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Original languageEnglish
Article numberjkab278
JournalG3: Genes, Genomes, Genetics
Issue number12
Publication statusPublished - 2021 Dec


  • Genetic prediction
  • Gene–environment interaction
  • Smooth thresholding

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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