Proc Natl Acad Sci U S A. 2026 Apr 7;123(14):e2600004123. doi: 10.1073/pnas.2600004123. Epub 2026 Mar 31.
ABSTRACT
Quantitative genetics is essential for genetic dissection of complex traits, yet the existing theory fails to illustrate a comprehensive landscape of genetic control mechanisms driving phenotypic variation and evolution. Here, we develop a statistical approach to assemble all genome loci into omnigenic interactome networks from diplotyped sequencing data. Such networks can not only capture dominance, epistasis, and pleiotropy and leverage these genetic concepts as bidirectional, signed, and weighted interactions among alleles and nonalleles, but also establish a framework for dissecting the genetic architecture of any single individual. While traditional approaches can only estimate coarse-grained genetic parameters at the population level, our approach can portray a fine-grained picture involving how each allele acts and interacts with every other allele for a single individual, thus facilitating its genome editing and genome engineering. By analyzing transcriptomic data of two diplotyped cultivars of a woody plant, our approach can interpret the genetic mechanisms underlying this species’ cold resistance and interorgan communication. Our network-centric approach, generalized as a graph statistics theory, builds the foundation of individualized quantitative genetics, a theory that can make genetics even more transformational to precision breeding or precision medicine.
PMID:41915744 | DOI:10.1073/pnas.2600004123
