Genetics of Exertional Heat Illness: Revealing New Associations and Expanding Heterogeneity.

Environmental heat stress represents a pervasive threat to warfighters, athletes, and occupational workers, impacting performance and increasing the risk of injury. Exertional heat illness (EHI) is a spectrum of clinical disorders of increasing severity. While frequently predictable, EHI can occur unexpectedly and may be followed by long-term comorbidities, including cardiovascular dysfunction and exercise intolerance. The objective of this study was to assess genetic factors contributing to EHI. Whole-exome sequencing was performed in a cohort of 53 cases diagnosed with EHI. Rare variants in prioritized gene sets were analyzed and classified per published guidelines. Clinically significant pathogenic and potentially pathogenic variants were identified in 30.2% of the study cohort. Variants were found in 14 genes, including the previously known