A spectral framework to map QTLs affecting joint differential networks of gene co-expression.

This work addresses a key gap in understanding the mechanistic foundations for genotype-phenotype associations. While existing expression quantitative trait loci (eQTL) methods identify candidate loci affecting gene expression variants, they often neglect the crucial role of gene co-expression networks. Here, we develop a network-based QTL framework to map genetic loci affecting the gene co-expression network. Utilizing a tensor-based spectral approach, our snQTL method estimates the differential co-expression patterns and effectively identifies the associated genetic loci. Application of snQTL to three-spined sticklebacks revealed candidate loci missed by standard methods. This work suggests the limitations of current approaches and highlights the potential of network-based functional loci discovery.