ObjectiveSleep disorders represent a serious global health challenge. However, the role of major environmental exposures, such as high-altitude hypoxia, and how they modify the influence of established risk factors across populations with differing susceptibility, remains poorly understood. This study aims to investigate the association between metabolic markers and sleep disorders under various environmental and adaptive conditions by comparing lowland residents with high-altitude populations (including high-altitude migrants reflecting environmental adaptation and indigenous Tibetans reflecting genetic adaptation).MethodsWe analyzed data from 5,220 participants after propensity score matching. Multivariable logistic regression, restricted cubic splines, and interaction analyses were employed to examine associations between metabolic indices and sleep disturbance, adjusted for sociodemographic and lifestyle factors.FindingsSleep disturbance prevalence differed significantly across populations (p < 0.001): lowlanders 14.9%, Plateau population 30.6% (migrants 35.0%, Tibetans 27.1%). Logistic regression revealed distinct risk patterns for sleep disturbance: plain-dwelling populations showed significant positive associations with all metabolic indices assessed (TyG index, TyG-WHtR, TyG-BMI, ABSI); The Plateau population as a whole showed significant positive associations with TyG, TyG-WHtR, and significant negative correlations with potassium; Tibetan highlanders exhibited associations only with TyG-related metabolic indicators (TyG, TyG -BMI, TyG-WHtR), with TyG exhibiting a unique nonlinear relationship; whereas plateau migrants were unrelated to other metabolic indicators except for a negative correlation with potassium. Among high-altitude migrants, depressive symptoms were associated with a stronger association between TyG-WHtR and sleep disorders; among Tibetans living at high altitudes, serum potassium was associated with a weaker association between anxiety and sleep disorders.ConclusionSleep disorders demonstrate heterogeneity across populations. High-altitude environments and genetic backgrounds are associated with sleep and with a modified effect of established risk factors.Clinical trial registrationhttps://www.chictr.org.cn/searchprojEN.html, identifier ChiCTR1900024623.