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
{"title":"炎症、白质结构和细胞外游离水的遗传关联。","authors":"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","doi":"10.1002/hbm.70101","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>T</sub>) 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<sub>p</sub> = -0.16, FDRp = 4.8 × 10<sup>-07</sup>; ρ<sub>g</sub> = -0.37 (0.12), FDRp = 0.01; TNFα: ρ<sub>p</sub> = -0.15, FDRp = 2.4 × 10<sup>-07</sup>; ρ<sub>g</sub> = -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<sub>p</sub> = -0.04, FDRp = 0.17; ρ<sub>g</sub> = -0.14 (0.13), FDRp = 0.29; TNFα: ρ<sub>p</sub> = -0.05, FDRp = 0.10; ρ<sub>g</sub> = -0.22 (0.13), FDRp = 0.10). There were significant phenotypic and genetic correlations between FW and both IL-8 (ρ<sub>p</sub> = 0.19, FDRp = 2.1 × 10<sup>-10</sup>; ρ<sub>g</sub> = 0.34 (0.11), FDRp = 0.01) and TNFα (ρ<sub>p</sub> = 0.16, FDRp = 1.89 × 10<sup>-07</sup>; ρ<sub>g</sub> = 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.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"46 1","pages":"e70101"},"PeriodicalIF":3.5000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic Associations Among Inflammation, White Matter Architecture, and Extracellular Free Water.\",\"authors\":\"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\",\"doi\":\"10.1002/hbm.70101\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sub>T</sub>) 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<sub>p</sub> = -0.16, FDRp = 4.8 × 10<sup>-07</sup>; ρ<sub>g</sub> = -0.37 (0.12), FDRp = 0.01; TNFα: ρ<sub>p</sub> = -0.15, FDRp = 2.4 × 10<sup>-07</sup>; ρ<sub>g</sub> = -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<sub>p</sub> = -0.04, FDRp = 0.17; ρ<sub>g</sub> = -0.14 (0.13), FDRp = 0.29; TNFα: ρ<sub>p</sub> = -0.05, FDRp = 0.10; ρ<sub>g</sub> = -0.22 (0.13), FDRp = 0.10). There were significant phenotypic and genetic correlations between FW and both IL-8 (ρ<sub>p</sub> = 0.19, FDRp = 2.1 × 10<sup>-10</sup>; ρ<sub>g</sub> = 0.34 (0.11), FDRp = 0.01) and TNFα (ρ<sub>p</sub> = 0.16, FDRp = 1.89 × 10<sup>-07</sup>; ρ<sub>g</sub> = 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.</p>\",\"PeriodicalId\":13019,\"journal\":{\"name\":\"Human Brain Mapping\",\"volume\":\"46 1\",\"pages\":\"e70101\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Human Brain Mapping\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/hbm.70101\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROIMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Brain Mapping","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/hbm.70101","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROIMAGING","Score":null,"Total":0}
Genetic Associations Among Inflammation, White Matter Architecture, and Extracellular Free Water.
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 (FAT) 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: 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). However, this relationship no longer reached significance when FA measures were derived using the two-compartment DTI model (IL-8: ρp = -0.04, FDRp = 0.17; ρg = -0.14 (0.13), FDRp = 0.29; TNFα: ρp = -0.05, FDRp = 0.10; ρg = -0.22 (0.13), FDRp = 0.10). There were significant phenotypic and genetic correlations between FW and both IL-8 (ρp = 0.19, FDRp = 2.1 × 10-10; ρg = 0.34 (0.11), FDRp = 0.01) and TNFα (ρp = 0.16, FDRp = 1.89 × 10-07; ρg = 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.
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.
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