Genome‐wide association study reveals the genetic architecture of drought tolerance in maize using yield‐based resistance indices and transcriptomic evidence

Drought is a major environmental factor limiting maize (Zea mays L.) production worldwide. Unraveling the genetic basis of drought tolerance and pinpointing key loci and candidate genes are fundamental to the molecular breeding of maize with enhanced drought resistance. In this research, 200 maize inbred lines were evaluated under two contrasting water conditions-water-stressed (WS) and well-watered-across two consecutive years (2022 and 2023). Grain yield and drought resistance index (DRI) at maturity were determined, with DRI serving as a yield-based index that provides a more comprehensive measure of drought tolerance. A genome-wide association study based on the FarmCPU model was conducted. A total of 126 significant single nucleotide polymorphisms were detected, including 43 associated with yield under WS conditions (phenotypic variance explained [PVE] = 4.64%-10.67%) and 55 related to DRI (PVE = 1.47%-10.67%). By combining two independent RNA-seq data collections, 43 core candidate genes were identified, 29 of which were functionally annotated. Gene Ontology enrichment and protein-protein interaction analyses demonstrated that these genes were primarily associated with biological processes related to metabolic regulation, signal transduction, and environmental stress responses. Notably, several transcription factors, including NAC35 (GRMZM5G813651), a MADS-box protein (GRMZM2G148693), and a C3HC4-type RING finger protein (GRMZM2G147319), have been previously implicated in drought response pathways. These findings provide new insights into the genetic architecture of drought tolerance in maize by using a mature-plant, yield-based DRI, which more directly reflects drought tolerance under field conditions.