Whole-genome resequencing reveals the polygenic architecture of dynamic laryngeal collapse in horses

<title>Abstract</title> <p> Complex performance traits often arise from the combined effects of numerous loci influencing multiple biological pathways, yet disentangling their genetic architecture remains challenging. Domestic animal populations offer powerful systems for studying such traits because artificial selection has generated marked phenotypic diversity while maintaining comparatively homogeneous genetic backgrounds. Dynamic laryngeal collapse (DLC), a performance-limiting upper airway disorder in horses associated with poll flexion, provides a natural model for investigating how distributed genomic variation contributes to multifactorial phenotypes involving neuromotor control, musculoskeletal function, and craniofacial morphology. Although previous SNP array analyses identified a suggestive locus on chromosome 7, the extent of genome-wide differentiation underlying susceptibility has remained unclear. To investigate the genetic architecture of DLC, we performed whole-genome resequencing of 43 Norwegian-Swedish Coldblooded Trotters (25 affected and 18 unaffected) and analysed allele frequency divergence using fixation index ( <italic>F</italic> _ST ) scans with 50 kb sliding windows and 25 kb steps. We identified 58 genome-wide significant regions ( <italic>F</italic> _ST &gt; 0.3) distributed across the genome, including replication of the previously reported chromosome 7 locus. Differentiated regions harbour genes involved in diverse but functionally connected processes, including neuromotor regulation ( <italic>ITPR1</italic> and <italic>ROBO1</italic> ), motor coordination and muscle tone ( <italic>RORA</italic> ), muscle contraction and force transmission ( <italic>TPM1</italic> and <italic>TLN2</italic> ), and craniofacial and airway development ( <italic>NR2F2</italic> ). Rather than supporting a single major-effect locus, these findings indicate coordinated differentiation across multiple biological systems contributing to phenotypic variation. Our results provide genome-wide evidence that susceptibility to DLC reflects coordinated differentiation across multiple loci spanning interacting neuromotor, musculoskeletal and developmental pathways rather than a single major-effect variant. By resolving the systems-level organisation of this complex phenotype, our findings demonstrate how population genomic analyses can reveal biologically coherent polygenic architectures that may remain obscured in conventional single-locus association studies. </p>