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Unhealthy sleep behaviors are associated with higher risks of osteoporosis (OP), while prospective evidence is limited. This study aimed to prospectively investigate this association, quantify the attributable burden of OP incidence reduction due to unhealthy sleep behaviors, and explore potential modifications by genetic risk factors. This longitudinal cohort study was conducted utilizing data from the UK Biobank, comprising 293,164 participants initially free of OP and with requisite sleep behaviors data at baseline. We followed the participants after recruitment until November 30, 2022, to ascertain incident OP. We assessed the associations of five sleep behaviors including sleep duration, chronotype, insomnia, daytime napping, and morning wake-up difficulties, as well as sleep behavior patterns identified based on the above sleep behaviors, with the risk of OP, using Cox models adjusted for multiple confounders. The analyses were then performed separately among individuals with different OP susceptibility, indexed by standard polygenetic risk scores(PRS) for OP. Our secondary outcome was OP with pathologic fracture. Subgroup and sensitivity analyses were performed. Additionally, attributable risk percent in the exposed population (AR%) and population attributable fraction (PAF) of sleep behaviors were calculated. Over a median follow-up of 13.7 years, 8253 new-onset OP cases were documented. Unhealthy sleep behaviors, such as long or short sleep duration, insomnia, daytime napping, morning wake-up difficulties, and unhealthy sleep patterns, were associated with elevated risks of OP (HRs ranging from 1.14 to 1.46, all P -value <0.001) compared to healthy sleep behaviors. Similar associations were observed for OP with pathologic fractures. Insomnia exhibited the largest AR% of 39.98 % (95%CI: 36.46, 43.31) and PAF of 33.25 % (95%CI: 30.00, 36.34) among healthy sleep patterns and components. A statistically significant multiplicative interaction was noted between sleep behaviors and OP PRS on OP risk (all P -interaction <0.001). Four unhealthy sleep behaviors and sleep behavior patterns were associated to increased OP risk, with insomnia contributing the most to OP incidence, while genetic risk for OP modified this association. These findings underscore the crucial role of adhering to healthy sleep behaviors for effective OP prevention. • Unhealthy sleep behaviors were associated with higher risks of osteoporosis. • Insomnia's attributable risk for osteoporosis was the highest among sleep behaviors. • Genetic risk modified the association between sleep behaviors and osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Neuroticism is a psychological personality trait that has a significant impact on public health and is also a potential predisposing factor for adverse disease outcomes; however, comprehensive studies of the subsequently developed conditions are lacking. The starting point of disease trajectory in terms of genetic variation remains unclear. Method: Our study included 344,609 adult participants from the UK Biobank cohort who were virtually followed up from January 1, 1997. Neuroticism levels were assessed using 12 items from the Eysenck Personality Questionnaire. We performed a phenome‐wide association analysis of neuroticism and subsequent diseases. Binomial tests and logistic regression models were used to test the temporal directionality and association between disease pairs to construct disease trajectories. We also investigated the association between polygenic risk scores (PRSs) for five psychiatric traits and high neuroticism. Results: The risk for 59 diseases was significantly associated with high neuroticism. Depression, anxiety, irritable bowel syndrome, migraine, spondylosis, and sleep disorders were the most likely to develop, with hazard ratios of 6.13, 3.66, 2.28, 1.74, 1.74, and 1.71, respectively. The disease trajectory network revealed two major disease clusters: cardiometabolic and chronic inflammatory diseases. Medium/high genetic risk groups stratified by the PRSs of four psychiatric traits were associated with an elevated risk of high neuroticism. We further identified eight complete phenotypic trajectory clusters of medium or high genetic risk for psychotic, anxiety‐, depression‐, and stress‐related disorders. Conclusion: Neuroticism plays an important role in the development of somatic and mental disorders. The full picture of disease trajectories from the genetic risk of psychiatric traits and neuroticism in early life to a series of diseases later provides evidence for future research to explore the etiological mechanisms and precision management. [ABSTRACT FROM AUTHOR]