WISER: an innovative and efficient method for correcting population structure in omics-based selection and association studies

Abstract

This work introduces WISER (whitening and successive least squares estimation refinement), an innovative and efficient method designed to enhance phenotype estimation by addressing population structure. WISER outperforms traditional methods such as least squares (LS) means and best linear unbiased prediction (BLUP) in phenotype estimation, offering a more accurate approach for omics-based selection and association studies. Unlike existing approaches which correct for population structure, WISER offers a generalized framework that can be applied across diverse experimental setups, species, and omics datasets, such as single nucleotide polymorphisms (SNPs), near-infrared spectroscopy (NIRS), and metabolomics. Within its framework, WISER extends classical methods that use eigen-information as fixed-effect covariates to correct for population structure, by relaxing their assumptions and implementing a true whitening matrix instead of a pseudo-whitening matrix. This approach corrects fixed effects (e.g., environmental effects) for the genetic covariance structure embedded within the experimental design, thereby removing confounding factors between fixed and genetic effects. To support its practical application, a user-friendly R package named wiser has been developed. The WISER method has been employed in analyses for genomic prediction and heritability estimation across four species and 33 traits using multiple datasets, including rice, maize, apple, and Scots pine. Results indicate that genomic predictive abilities based on WISER-estimated phenotypes consistently outperform the LS-means and BLUP approaches for phenotype estimation, regardless of the predictive model applied. This underscores WISERs potential to advance omics analyses and related research fields by capturing stronger genetic signals.