Obstructive sleep apnea and structural and functional brain alterations: a brain-wide investigation from clinical association to genetic causality

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 27, 2025

Obstructive sleep apnea (OSA) is linked to brain alterations, but the specific regions affected and causal associations between these changes remain unclear. We studied 20 pairs of age-, sex-, BMI-, education- matched OSA patients healthy controls using multimodal magnetic resonance imaging (MRI) from August 2019 February 2020. Additionally, large-scale Mendelian randomization analyses were performed genome-wide association study (GWAS) data on 3935 imaging-derived phenotypes (IDPs), assessed in up 33,224 individuals December 2023 March 2024, explore potential genetic causality alterations whole structure function. In cohort study, exhibited significantly lower fractional amplitude low-frequency fluctuation regional homogeneity right posterior cerebellar lobe bilateral superior middle frontal gyrus, while showing higher levels left occipital central gyrus. Decreased anisotropy (FA) increased apparent diffusion coefficient (ADC) was shown longitudinal fasciculus. According results Affiliation file 2: table s6, it ADC value fasciculus a positive correlation with lowest oxygen saturation. analyses, area inferior temporal sulcus (OR: 0.89; 95% CI: 0.82-0.96), rfMRI connectivity ICA100 edge 893 0.88; 951 0.82-0.97), 1213 0.82-0.96) decreased OSA. Conversely, mean thickness G-front-inf-Triangul hemisphere 1.14; 1.05-1.23), orientation dispersion index tapetum 1.13; 1.04-1.23), 258 1.04-1.22) showed opposite results. Nerve fiber damage imbalances neuronal activity across multiple caused by hypoxia, particularly lobe, underlie structural functional impairments

Language: Английский

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Brain-wide pleiotropy investigation of alcohol drinking and tobacco smoking behaviors

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 20, 2025

To investigate the pleiotropic mechanisms linking brain structure and function to alcohol drinking tobacco smoking, we integrated genome-wide data generated by GWAS Sequencing Consortium of Alcohol Nicotine use (GSCAN; up 805,431 participants) with information related 3935 imaging-derived phenotypes (IDPs) available from UK Biobank (N = 33,224). We observed global genetic correlation smoking behaviors white matter hyperintensities, morphology superior longitudinal fasciculus, mean thickness pole-occipital. With respect latter IDP, identified a local age at which individual began regularly (hg38 chr2:35,895,678-36,640,246: rho 1, p 1.01 × 10-5). This region has been previously associated initiation, educational attainment, chronotype, cortical thickness. Our genetically informed causal inference analysis using both latent variable approach Mendelian randomization linked activity prefrontal premotor cortex that inferior precentral sulci, cingulate sulci number alcoholic drinks per week (genetic causality proportion, gcp 0.38, 8.9 10-4, -0.18 ± 0.07; inverse variance weighting, IVW beta -0.04, 95%CI -0.07--0.01). relationship could be role these regions in modulation reward-seeking motivation processing social cues. Overall, our brain-wide investigation highlighted different likely contribute suggesting decision-making activities chemosensory as modulators propensity towards consumption.

Language: Английский

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Integration of metabolomic and brain-imaging data highlights pleiotropy among posttraumatic stress disorder, glycoprotein acetyls, and pallidum structure

Biological Psychiatry Global Open Science, Journal Year: 2025, Volume and Issue: unknown, P. 100482 - 100482

Published: March 1, 2025

The development of posttraumatic stress disorder (PTSD) is attributable to the interplay between exposure severe traumatic events, environmental factors, and biological characteristics. Blood brain imaging markers have been associated with PTSD. However, our knowledge, no study has systematically investigated genetic relationship PTSD, metabolic biomarkers, brainwide imaging. We integrated genome-wide data informative 233 3935 imaging-derived phenotypes (IDPs). Pleiotropy was assessed by applying global local correlation, colocalization, genetically inferred causality. observed significant overlap PTSD glycoprotein acetyls (GlycA) (a stable inflammatory biomarker) in 2 independent cohorts (discovery r g = 0.26, p 1.00 × 10-4; replication 0.23, 5.99 10-19). Interestingly, there correlation anxiety GlycA (p .33). were both correlated median T2∗ left pallidum (IDP-1444: 0.14, 1.39 10-5; -0.38, 2.50 10-3, respectively). Local 7 regions < 2.0 10-5), mapping genes related immune response, inflammation, processes. Furthermore, we identified 1 variant, rs12048743, evidence horizontal pleiotropy linking IDP-1444 (z 17.14, z -6.07, theta 2.06 10-8). Regional colocalization among GlycA, IDP-1444, tissue-specific transcriptomic regulation for frontal cortex testis (rs12048743-chr1q32.1; posterior probability > 0.8). While also tested causality metabolomic IDPs, these not consistent across different informed causal inference methods. Our findings highlight a new putative pleiotropic mechanism that links systemic inflammation structure

Language: Английский

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Polygenic Risk Score-Based Association Analysis Identifies Genetic Comorbidities Associated with Age-Related Hearing Difficulty in Two Independent Samples

Journal of the Association for Research in Otolaryngology, Journal Year: 2024, Volume and Issue: 25(4), P. 387 - 406

Published: May 23, 2024

Language: Английский

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Brain-wide pleiotropy investigation of alcohol drinking and tobacco smoking behaviors

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 28, 2024

ABSTRACT To investigate the pleiotropic mechanisms linking brain structure and function to alcohol drinking tobacco smoking, we integrated genome-wide data generated by GWAS Sequencing Consortium of Alcohol Nicotine use (GSCAN; up 805,431 participants) with information related 3,935 imaging-derived phenotypes (IDPs) available from UK Biobank (N=33,224). We observed global genetic correlation smoking behaviors white matter hyperintensities, morphology superior longitudinal fasciculus, mean thickness pole-occipital. With respect latter IDP, identified a local age at which individual began regularly (hg38 chr2:35,895,678-36,640,246: rho=1, p=1.01×10 −5 ). This region has been previously associated initiation, educational attainment, chronotype, cortical thickness. Our genetically informed causal inference analysis using both latent variable approach Mendelian randomization linked activity prefrontal premotor cortex that inferior precentral sulci, cingulate sulci number alcoholic drinks per week (genetic causality proportion, gcp=0.38, p=8.9×10 −4 , rho=-0.18±0.07; inverse variance weighting, IVW beta=-0.04, 95%CI=-0.07 – −0.01). relationship could be role these regions in modulation reward-seeking motivation processing social cues. Overall, our brain-wide investigation highlighted different likely contribute suggesting decision-making activities chemosensory as modulators propensity towards consumption.

Language: Английский

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Genetic evidence supports a causal relationship between air pollution and brain imaging-derived phenotypes

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 281, P. 116664 - 116664

Published: July 1, 2024

Observational studies have reported associations between air pollutants and brain imaging-derived phenotypes (IDPs); however, whether this relationship is causal remains uncertain.

Language: Английский

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