Qiu Haoyuan, Shi Miao, Zhong Zicheng, Hu Haoran, Sang Hunini, Zhou Meijuan, Feng Zhijun
School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China.
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Biomedicines. 2024 Aug 16;12(8):1874. doi: 10.3390/biomedicines12081874.
This study employed a two-step Mendelian randomization analysis to explore the causal relationship between telomere length, as a marker of aging, and anorexia nervosa and to evaluate the mediating role of changes in the white matter microstructure across different brain regions. We selected genetic variants associated with 675 diffusion magnetic resonance imaging phenotypes representing changes in brain white matter. F-statistics confirmed the validity of the instruments, ensuring robust causal inference. Sensitivity analyses, including heterogeneity tests, horizontal pleiotropy tests, and leave-one-out tests, validated the results. The results show that telomere length is significantly negatively correlated with anorexia nervosa in a unidirectional manner ( = 0.017). Additionally, changes in specific white matter structures, such as the internal capsule, corona radiata, posterior thalamic radiation, left cingulate gyrus, left longitudinal fasciculus, and left forceps minor ( < 0.05), were identified as mediators. These findings enhance our understanding of the neural mechanisms, underlying the exacerbation of anorexia nervosa with aging; emphasize the role of brain functional networks in disease progression; and provide potential biological targets for future therapeutic interventions.
本研究采用两步孟德尔随机化分析，以探讨作为衰老标志物的端粒长度与神经性厌食症之间的因果关系，并评估不同脑区白质微观结构变化的中介作用。我们选择了与代表脑白质变化的675种扩散磁共振成像表型相关的基因变异。F统计量证实了工具变量的有效性，确保了可靠的因果推断。敏感性分析，包括异质性检验、水平多效性检验和留一法检验，验证了结果。结果表明，端粒长度与神经性厌食症呈显著负相关（单向关联，P = 0.017）。此外，特定白质结构的变化，如内囊、放射冠、丘脑后辐射、左侧扣带回、左侧纵束和左侧小钳状束（P < 0.05），被确定为中介因素。这些发现加深了我们对随着年龄增长神经性厌食症加重背后神经机制的理解；强调了脑功能网络在疾病进展中的作用；并为未来的治疗干预提供了潜在的生物学靶点。
