Genetic Associations Among Inflammation, White Matter Architecture, and Extracellular Free Water.

IF 3.5 2区医学 Q1 NEUROIMAGING Human Brain Mapping Pub Date : 2025-01-01 DOI:10.1002/hbm.70101

Amanda L Rodrigue, Emma E M Knowles, Josephine Mollon, Samuel R Mathias, Juan Manuel Peralta, Ana C Leandro, Peter T Fox, Peter Kochunov, Rene L Olvera, Laura Almasy, Joanne E Curran, John Blangero, David C Glahn

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Abstract

Phenotypic and genetic relationships between white matter microstructure (i.e., fractional anisotropy [FA]) and peripheral inflammatory responses (i.e., circulating cytokines) have important implications for health and disease. However, it is unclear whether previously discovered genetic correlations between the two traits are due to tissue-specific white matter architecture or increased free water in the extracellular space. We applied a two-compartment model to diffusion tensor imaging (DTI) data and estimated tissue-specific white matter microstructure (FA_T) and free water volume (FW). We then quantified their heritability and their genetic correlations with two peripherally circulating proinflammatory cytokines (IL-8 and TNFα), and compared these correlations to those obtained using traditional FA measures from one-compartment DTI models. All DTI and cytokine measures were significantly moderately heritable. We confirmed phenotypic and genetic correlations between circulating cytokine levels and single-compartment FA across the brain (IL-8: ρ_p = -0.16, FDRp = 4.8 × 10^-07; ρ_g = -0.37 (0.12), FDRp = 0.01; TNFα: ρ_p = -0.15, FDRp = 2.4 × 10^-07; ρ_g = -0.34 (0.12), p = 0.01). However, this relationship no longer reached significance when FA measures were derived using the two-compartment DTI model (IL-8: ρ_p = -0.04, FDRp = 0.17; ρ_g = -0.14 (0.13), FDRp = 0.29; TNFα: ρ_p = -0.05, FDRp = 0.10; ρ_g = -0.22 (0.13), FDRp = 0.10). There were significant phenotypic and genetic correlations between FW and both IL-8 (ρ_p = 0.19, FDRp = 2.1 × 10^-10; ρ_g = 0.34 (0.11), FDRp = 0.01) and TNFα (ρ_p = 0.16, FDRp = 1.89 × 10^-07; ρ_g = 0.30 (0.12), FDRp = 0.02). These results have important implications for understanding the mechanisms linking the two phenomena, but they also serve as a cautionary note for those examining associations between white matter integrity using single-compartment models and inflammatory processes.

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炎症、白质结构和细胞外游离水的遗传关联。

白质微结构（即分数各向异性[FA]）与外周炎症反应（即循环细胞因子）之间的表型和遗传关系对健康和疾病具有重要意义。然而，尚不清楚先前发现的这两种性状之间的遗传相关性是由于组织特异性白质结构还是细胞外空间自由水的增加。我们对扩散张量成像（DTI）数据应用了双室模型，并估计了组织特异性白质微观结构（FAT）和自由水体积（FW）。然后，我们量化了它们的遗传性及其与两种外周循环促炎细胞因子（IL-8和tnf - α）的遗传相关性，并将这些相关性与使用单室DTI模型的传统FA测量结果进行了比较。所有DTI和细胞因子指标均具有显著的中度遗传性。我们证实了循环细胞因子水平与全脑单室FA之间的表型和遗传相关性(IL-8: ρp = -0.16, FDRp = 4.8 × 10-07；ρg = -0.37 (0.12), FDRp = 0.01；TNFα: ρp = -0.15, FDRp = 2.4 × 10-07；ρg = -0.34 (0.12), p = 0.01)。然而，当使用双室DTI模型推导FA测量时，这种关系不再达到显著性(IL-8: ρp = -0.04, FDRp = 0.17；ρg = -0.14 (0.13), FDRp = 0.29；TNFα: ρp = -0.05, FDRp = 0.10；ρ = -0.22 (0.13), FDRp = 0.10)。FW与IL-8均存在显著的表型和遗传相关(ρp = 0.19, FDRp = 2.1 × 10-10；ρ= 0.34 (0.11),FDRp = 0.01)和肿瘤坏死因子αρp = 0.16, FDRp = 1.89×10-07;ρg = 0.30 (0.12), FDRp = 0.02)。这些结果对于理解这两种现象之间的联系机制具有重要意义，但对于那些使用单室模型研究白质完整性与炎症过程之间关系的人来说，它们也起到了警示作用。

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来源期刊

Human Brain Mapping 医学-核医学

CiteScore

8.30

自引率

6.20%

发文量

401

审稿时长

3-6 weeks

期刊介绍： Human Brain Mapping publishes peer-reviewed basic, clinical, technical, and theoretical research in the interdisciplinary and rapidly expanding field of human brain mapping. The journal features research derived from non-invasive brain imaging modalities used to explore the spatial and temporal organization of the neural systems supporting human behavior. Imaging modalities of interest include positron emission tomography, event-related potentials, electro-and magnetoencephalography, magnetic resonance imaging, and single-photon emission tomography. Brain mapping research in both normal and clinical populations is encouraged. Article formats include Research Articles, Review Articles, Clinical Case Studies, and Technique, as well as Technological Developments, Theoretical Articles, and Synthetic Reviews. Technical advances, such as novel brain imaging methods, analyses for detecting or localizing neural activity, synergistic uses of multiple imaging modalities, and strategies for the design of behavioral paradigms and neural-systems modeling are of particular interest. The journal endorses the propagation of methodological standards and encourages database development in the field of human brain mapping.