From paradox to biology: shared genetic architecture underlies the inverse association between smoking and Sjögren's disease.

The phrase “high-altitude environment” generally denotes low-pressure, low-oxygen conditions at elevations above 3,000 m, where the partial pressure of oxygen is markedly lower than in lowland regions. Athletes training at high elevations must contend with both environmental hypoxia and physical exertion. Prolonged environmental exposure induces the body to establish compensating physiological adaptations, enhancing the efficiency of oxygen transport and consumption, hence influencing overall sports performance. In competitive sports, exceptional athletic performance relies not just on peripheral musculoskeletal function but also significantly on the central nervous system’s capacity for rapid decision-making, movement planning, and control coordination under time constraints. The prefrontal cortex (PFC), premotor cortex (PMC), supplementary motor area (SMA), and primary motor cortex (M1) constitute essential brain regions involved in motor control, forming a comprehensive neural circuit encompassing motor decision-making, motor integration, and motor output. The synchronicity of spontaneous activity across brain regions during rest, known as resting-state functional connectivity (RSFC), reflects the brain’s intrinsic network organization and its capacity for information transfer. The brain’s energy expenditure during rest is almost identical to that during task execution; thus, its resting-state network activity can be considered a baseline reserve for task-related functions. In recent years, functional near-infrared spectroscopy (fNIRS) has emerged as a significant tool for examining brain networks, owing to its non-invasive nature, high temporal resolution, and ecological validity. fNIRS can indirectly indicate neuronal activity intensity and hemodynamic coordination between brain regions by monitoring the dynamic fluctuations in the concentrations of oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) in the cerebral cortex, based on the neurovascular coupling (NVC) mechanism. Environmental factors and ethnic genetic background exert a profound combined regulatory effect on athletes’ physiological functions. The Tibetan population, residing on the plateau for generations, has evolved a distinct physiological phenotype through protracted natural selection. Research indicates that the Tibetan population, influenced by particular genetic variants such as the EPAS1 gene, has evolved heightened oxygen affinity and microcirculatory efficiency, while diminishing their dependence on compensatory erythropoiesis, and demonstrating distinct cerebral blood flow distribution strategies and baseline cerebral metabolism. Nonetheless, a substantial gap persists in research concerning the impact of varying altitudinal exposure histories and ethnic backgrounds on brain functional connectivity in athletes, especially regarding adolescent athletes—a demographic undergoing a crucial phase of brain development and plasticity. Prolonged sport-specific training has been demonstrated to substantially remodel the brain’s fundamental motor networks. Nonetheless, it remains unclear which organizational traits these brain networks will exhibit when exercise-induced neuroplasticity interacts with genetic or metabolic changes associated with high-altitude life. This study employed a cross-sectional design and fNIRS to compare resting-state brain connectivity patterns in young male soccer players—specifically, Tibetan men from high-altitude regions and Han men from lowland areas—who possess equivalent athletic levels and specialized training backgrounds, yet are situated in a lowland environment. This study aims to investigate intrinsic organizational differences in the prefrontal and core motor networks between these two populations, which have distinct living environments and ethnic genetic backgrounds, while controlling for systemic peripheral physiological covariates such as heart rate and blood oxygen levels. The study hypothesizes that Tibetan and Han athletes exhibit systematic differences in resting-state brain connectivity patterns, and that these differences are not solely determined by physical hypoxia, but rather by an underlying neural phenotype shaped by a combination of specific genetic backgrounds, long-term metabolic and hemodynamic adaptations, and athletic training. This not only contributes to the neuroscientific understanding of the interaction between adaptation to extreme environments and brain functional plasticity, but also provides an important baseline reference for the scientific assessment of adolescent athletes from diverse backgrounds.