Obstructive sleep apnea and structural and functional brain alterations: a brain-wide investigation from clinical association to genetic causality
Abstract Background Obstructive sleep apnea (OSA) is linked to brain alterations, but the specific regions affected and the causal associations between these changes remain unclear. Methods We studied 20 pairs of age-, sex-, BMI-, and education- matched OSA patients and healthy controls using multim...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12916-025-03876-8 |
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| author | Kang Wu Qiming Gan Yuhong Pi Yanjuan Wu Wenjin Zou Xiaofen Su Sun Zhang Xinni Wang Xinchun Li Nuofu Zhang |
| author_facet | Kang Wu Qiming Gan Yuhong Pi Yanjuan Wu Wenjin Zou Xiaofen Su Sun Zhang Xinni Wang Xinchun Li Nuofu Zhang |
| author_sort | Kang Wu |
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| description | Abstract Background Obstructive sleep apnea (OSA) is linked to brain alterations, but the specific regions affected and the causal associations between these changes remain unclear. Methods We studied 20 pairs of age-, sex-, BMI-, and education- matched OSA patients and healthy controls using multimodal magnetic resonance imaging (MRI) from August 2019 to February 2020. Additionally, large-scale Mendelian randomization analyses were performed using genome-wide association study (GWAS) data on OSA and 3935 brain imaging-derived phenotypes (IDPs), assessed in up to 33,224 individuals between December 2023 and March 2024, to explore potential genetic causality between OSA and alterations in whole brain structure and function. Results In the cohort study, OSA patients exhibited significantly lower fractional amplitude of low-frequency fluctuation and regional homogeneity in the right posterior cerebellar lobe and bilateral superior and middle frontal gyrus, while showing higher levels in the left occipital lobe and left posterior central gyrus. Decreased fractional anisotropy (FA) but increased apparent diffusion coefficient (ADC) was shown in the bilateral superior longitudinal fasciculus. According to the results of Affiliation file 2: table s6, it is the ADC value of right superior longitudinal fasciculus was shown a positive correlation with the lowest oxygen saturation. In the Mendelian randomization analyses, the area of left inferior temporal sulcus (OR: 0.89; 95% CI: 0.82–0.96), rfMRI connectivity ICA100 edge 893 (OR: 0.88; 95% CI: 0.82–0.96), ICA100 edge 951 (OR: 0.89; 95% CI: 0.82–0.97), and ICA100 edge 1213 (OR: 0.89; 95% CI: 0.82–0.96) were significantly decreased in OSA. Conversely, mean thickness of G-front-inf-Triangul in right hemisphere (OR: 1.14; 95% CI: 1.05–1.23), mean orientation dispersion index in right tapetum (OR: 1.13; 95% CI: 1.04–1.23), and rfMRI connectivity ICA100 edge 258 (OR: 1.13; 95% CI: 1.04–1.22) showed opposite results. Conclusions Nerve fiber damage and imbalances in neuronal activity across multiple brain regions caused by hypoxia, particularly the frontal lobe, underlie the structural and the functional connectivity impairments in OSA. |
| format | Article |
| id | doaj-art-5f72a9cd7e6a4b369776fde844e5566b |
| institution | Kabale University |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj-art-5f72a9cd7e6a4b369776fde844e5566b2025-02-02T12:28:12ZengBMCBMC Medicine1741-70152025-01-0123111110.1186/s12916-025-03876-8Obstructive sleep apnea and structural and functional brain alterations: a brain-wide investigation from clinical association to genetic causalityKang Wu0Qiming Gan1Yuhong Pi2Yanjuan Wu3Wenjin Zou4Xiaofen Su5Sun Zhang6Xinni Wang7Xinchun Li8Nuofu Zhang9Sleep Medicine Center, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversitySleep Medicine Center, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversitySleep Medicine Center, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversitySleep Medicine Center, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityThe Affiliated Brain Hospital of Guangzhou Medical UniversitySleep Medicine Center, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversitySleep Medicine Center, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversitySleep Medicine Center, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Radiology, The First Affiliated Hospital of Guangzhou Medical UniversitySleep Medicine Center, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityAbstract Background Obstructive sleep apnea (OSA) is linked to brain alterations, but the specific regions affected and the causal associations between these changes remain unclear. Methods We studied 20 pairs of age-, sex-, BMI-, and education- matched OSA patients and healthy controls using multimodal magnetic resonance imaging (MRI) from August 2019 to February 2020. Additionally, large-scale Mendelian randomization analyses were performed using genome-wide association study (GWAS) data on OSA and 3935 brain imaging-derived phenotypes (IDPs), assessed in up to 33,224 individuals between December 2023 and March 2024, to explore potential genetic causality between OSA and alterations in whole brain structure and function. Results In the cohort study, OSA patients exhibited significantly lower fractional amplitude of low-frequency fluctuation and regional homogeneity in the right posterior cerebellar lobe and bilateral superior and middle frontal gyrus, while showing higher levels in the left occipital lobe and left posterior central gyrus. Decreased fractional anisotropy (FA) but increased apparent diffusion coefficient (ADC) was shown in the bilateral superior longitudinal fasciculus. According to the results of Affiliation file 2: table s6, it is the ADC value of right superior longitudinal fasciculus was shown a positive correlation with the lowest oxygen saturation. In the Mendelian randomization analyses, the area of left inferior temporal sulcus (OR: 0.89; 95% CI: 0.82–0.96), rfMRI connectivity ICA100 edge 893 (OR: 0.88; 95% CI: 0.82–0.96), ICA100 edge 951 (OR: 0.89; 95% CI: 0.82–0.97), and ICA100 edge 1213 (OR: 0.89; 95% CI: 0.82–0.96) were significantly decreased in OSA. Conversely, mean thickness of G-front-inf-Triangul in right hemisphere (OR: 1.14; 95% CI: 1.05–1.23), mean orientation dispersion index in right tapetum (OR: 1.13; 95% CI: 1.04–1.23), and rfMRI connectivity ICA100 edge 258 (OR: 1.13; 95% CI: 1.04–1.22) showed opposite results. Conclusions Nerve fiber damage and imbalances in neuronal activity across multiple brain regions caused by hypoxia, particularly the frontal lobe, underlie the structural and the functional connectivity impairments in OSA.https://doi.org/10.1186/s12916-025-03876-8Obstructive sleep apneaBrain structure and functionNeuroimagingMendelian randomization |
| spellingShingle | Kang Wu Qiming Gan Yuhong Pi Yanjuan Wu Wenjin Zou Xiaofen Su Sun Zhang Xinni Wang Xinchun Li Nuofu Zhang Obstructive sleep apnea and structural and functional brain alterations: a brain-wide investigation from clinical association to genetic causality BMC Medicine Obstructive sleep apnea Brain structure and function Neuroimaging Mendelian randomization |
| title | Obstructive sleep apnea and structural and functional brain alterations: a brain-wide investigation from clinical association to genetic causality |
| title_full | Obstructive sleep apnea and structural and functional brain alterations: a brain-wide investigation from clinical association to genetic causality |
| title_fullStr | Obstructive sleep apnea and structural and functional brain alterations: a brain-wide investigation from clinical association to genetic causality |
| title_full_unstemmed | Obstructive sleep apnea and structural and functional brain alterations: a brain-wide investigation from clinical association to genetic causality |
| title_short | Obstructive sleep apnea and structural and functional brain alterations: a brain-wide investigation from clinical association to genetic causality |
| title_sort | obstructive sleep apnea and structural and functional brain alterations a brain wide investigation from clinical association to genetic causality |
| topic | Obstructive sleep apnea Brain structure and function Neuroimaging Mendelian randomization |
| url | https://doi.org/10.1186/s12916-025-03876-8 |
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