We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Varicella is a vaccine-preventable infectious disease. Since 1 December 2018, the varicella vaccine has been included in the local Expanded Programme on Immunization (EPI) in Wuxi, China, and children born after 1 December 2014 are eligible for free vaccination. To evaluate the effect of varicella vaccination in Wuxi city, we selected 382 397 children born from 2012 to 2016 as subjects. Their disease data were obtained from the Chinese Disease Prevention and Control Information System, and their vaccination data were obtained from the Jiangsu Province Vaccination Integrated Service Management Information System. The incidence of breakthrough varicella cases increased in the first 4 years and reached the peak in the fifth year. With the increase of vaccination rate, the incidence of varicella decreased significantly. The vaccine effectiveness (VE) was found to be 88.17%–95.78% for one dose and 98.65%–99.93% for two doses. Although the VE per dose decreased from 99.57% in the first year to 93.04% in the eighth year, it remained high. These findings confirmed the effectiveness of varicella vaccination in children, supported the use of a two-dose varicella vaccination strategy to achieve better protection, and provided important insights into the optimal vaccination strategy for varicella prevention in children.
Numerous studies have indicated that turbulence typically initiates along the boundary layer of the stationary disk within a rotor–stator cavity. To describe the transition process to turbulence on the stationary side of a closed rotor–stator cavity, a comprehensive approach combining global linear stability analysis with direct numerical simulation was adopted in the present study. The proposed model aligns with that of Yim et al. (J. Fluid Mech., vol. 848, 2018, pp. 631–647), who investigated the stability characteristics of the rotating-disk boundary layer in a rotor–stator cavity. In order to achieve a stable inflow for the stationary-disk boundary layer, we rotate the shroud together with the rotating disk. Through careful global stability analysis, the predominant spiral mode exhibiting the highest instability in the boundary layer of the stationary disk was discerned, corroborating observations from simulations. Initially, the spiral mode undergoes linear amplification, reaches a state of linear saturation and enters the nonlinear regime. Following nonlinear saturation in the flow field, a circular wave mode arises due to the influence of mean flow distortion. As the Reynolds number attained a sufficiently high level, the interplay between the downstream-propagating circular mode and spiral mode amplified disturbances in the boundary layer of the stationary disk, ultimately leading to the development of localised turbulence at the mid-radius of the rotor–stator cavity. Notably, the present study is the first to elucidate the coexistence of laminar–transitional–turbulent flow states in the stationary-disk boundary layer through direct numerical simulations.
Whether material deprivation-related childhood socio-economic disadvantages (CSD) and care-related adverse childhood experiences (ACE) have different impacts on depressive symptoms in middle-aged and older people is unclear.
Methods
In the Guangzhou Biobank Cohort Study, CSD and ACE were assessed by 7 and 5 culturally sensitive questions, respectively, on 8,716 participants aged 50+. Depressive symptoms were measured by 15-item Geriatric Depression Scale (GDS). Multivariable linear regression, stratification analyses, and mediation analyses were done.
Results
Higher CSD and ACE scores were associated with higher GDS score in dose-response manner (P for trend <0.001). Participants with one point increment in CSD and ACE had higher GDS score by 0.11 (95% confidence interval [CI], 0.09–0.14) and 0.41 (95% CI, 0.35–0.47), respectively. The association of CSD with GDS score was significant in women only (P for sex interaction <0.001; women: β (95% CI)=0.14 (0.11–0.17), men: 0.04 (−0.01 to 0.08)). The association between ACE and GDS score was stronger in participants with high social deprivation index (SDI) (P for interaction = 0.01; low SDI: β (95% CI)=0.36 (0.29–0.43), high SDI: 0.64 (0.48–0.80)). The proportion of association of CSD and ACE scores with GDS score mediated via education was 20.11% and 2.28%.
Conclusions
CSD and ACE were associated with late-life depressive symptoms with dose-response patterns, especially in women and those with low adulthood socio-economic status. Education was a major mediator for CSD but not ACE. Eliminating ACE should be a top priority.
Electron backscatter diffraction (EBSD) has been widely used in recent studies of eggshells for its convenience in collecting in situ crystallographic information. China has a wide variety of dinosaur eggshells, although nearly none have been studied with this technique. Elongatoolithid eggs include many oogenera, although the microstructural differences of some were not highly appreciated, leading to several parataxonomic problems. In this paper, we surveyed seven elongatoolithid oogenera in China using EBSD in order to acquire more information about their microstructural variation. It is shown in this paper that in some elongatoolithid eggshells, scaly calcite grains that form the squamatic ultrastructure are not the only form of calcite in the continuous layer. Large columnar grains separated by high-angled grain boundaries and slender subgrains separated by radially arranged low-angled grain boundaries could exist in certain areas of the eggshells such as Macroolithus and Macroelongatoolithus. This paper discusses the criteria for identifying squamatic ultrastructure and proposes type I (rich in rugged high-angled grain boundaries) and type II (rich in both rugged high- and low-angled grain boundaries) squamatic ultrastructures. A pathological layer is found in Undulatoolithus pengi. An external zone is identified in the eggshell of Heishanoolithus changii, which does not support its position within the oofamily Elongatoolithidae. We argue that Paraelongatoolithus no longer belongs to Elongatoolithidae based on a combination of reticulated ornamentation, columnar continuous layer, and acicular mammillae. The high structural variation in elongatoolithid eggshells also implies that it may be inappropriate to relate all previous elongatoolithid eggshells to oviraptorosaurs and assume they are non-monophyletic.
The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear.
Methods
By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders.
Results
SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07–1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06–1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04–1.18, p = 1.84 × 10−3).
Conclusions
We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.
Although dopaminergic disturbances are well-known in schizophrenia, the understanding of dopamine-related brain dynamics remains limited. This study investigates the dynamic coactivation patterns (CAPs) associated with the substantia nigra (SN), a key dopaminergic nucleus, in first-episode treatment-naïve patients with schizophrenia (FES).
Methods
Resting-state fMRI data were collected from 84 FES and 94 healthy controls (HCs). Frame-wise clustering was implemented to generate CAPs related to SN activation or deactivation. Connectome features of each CAP were derived using an edge-centric method. The occurrence for each CAP and the balance ratio for antagonistic CAPs were calculated and compared between two groups, and correlations between temporal dynamic metrics and symptom burdens were explored.
Results
Functional reconfigurations in CAPs exhibited significant differences between the activation and deactivation states of SN. During SN activation, FES more frequently recruited a CAP characterized by activated default network, language network, control network, and the caudate, compared to HCs (F = 8.54, FDR-p = 0.030). Moreover, FES displayed a tilted balance towards a CAP featuring SN-coactivation with the control network, caudate, and thalamus, as opposed to its antagonistic CAP (F = 7.48, FDR-p = 0.030). During SN deactivation, FES exhibited increased recruitment of a CAP with activated visual and dorsal attention networks but decreased recruitment of its opposing CAP (F = 6.58, FDR-p = 0.034).
Conclusion
Our results suggest that neuroregulatory dysfunction in dopaminergic pathways involving SN potentially mediates aberrant time-varying functional reorganizations in schizophrenia. This finding enriches the dopamine hypothesis of schizophrenia from the perspective of brain dynamics.
Over the past several decades, more research focuses have been made on the inflammation/immune hypothesis of schizophrenia. Building upon synaptic plasticity hypothesis, inflammation may contribute the underlying pathophysiology of schizophrenia. Yet, pinpointing the specific inflammatory agents responsible for schizophrenia remains a complex challenge, mainly due to medication and metabolic status. Multiple lines of evidence point to a wide-spread genetic association across genome underlying the phenotypic variations of schizophrenia.
Method
We collected the latest genome-wide association analysis (GWAS) summary data of schizophrenia, cytokines, and longitudinal change of brain. We utilized the omnigenic model which takes into account all genomic SNPs included in the GWAS of trait, instead of traditional Mendelian randomization (MR) methods. We conducted two round MR to investigate the inflammatory triggers of schizophrenia and the resulting longitudinal changes in the brain.
Results
We identified seven inflammation markers linked to schizophrenia onset, which all passed the Bonferroni correction for multiple comparisons (bNGF, GROA(CXCL1), IL-8, M-CSF, MCP-3 (CCL7), TNF-β, CRP). Moreover, CRP were found to significantly influence the linear rate of brain morphology changes, predominantly in the white matter of the cerebrum and cerebellum.
Conclusion
With an omnigenic approach, our study sheds light on the immune pathology of schizophrenia. Although these findings need confirmation from future studies employing different methodologies, our work provides substantial evidence that pervasive, low-level neuroinflammation may play a pivotal role in schizophrenia, potentially leading to notable longitudinal changes in brain morphology.
Binary nanodroplet collisions have received increasing attention, whilst the identification of collision outcomes and the viscous dissipation mechanism have remained poorly understood. Using molecular dynamics simulations, this study investigates binary nanodroplet collisions over wide ranges of Weber number (We), Ohnesorge number (Oh) and off-centre distances. Coalescence, stretching separation and shattering are identified; however, bouncing, reflexive separation and rotational separation reported for millimetre-sized collisions are not observed, which is attributed to the enhanced viscous effect caused by the ‘natural’ high-viscosity characteristics of nanodroplets. Intriguingly, as an intermediate outcome, holes form in retracting films at relatively high We, arising from the vibration and thermal fluctuation of the films. Due to the combined effects of inertial, capillary and viscous forces, binary nanodroplet collisions fall into the cross-over regime, so estimating viscous dissipation becomes extremely important for distinguishing outcome boundaries. Based on the criterion that stretching separation is triggered only when the residual off-centre kinetic energy exceeds the surface energy required for separation, the boundary equation between coalescence and stretching separation is established. Here, viscous dissipation is calculated by the extracted flow feature from simulations, showing that the ratio of viscous dissipation to the initial kinetic energy depends only on Oh, not on We. Because of complex viscous dissipation mechanisms, the same boundary equation in the cross-over regime has also not been satisfactorily revealed for macroscale collisions. Therefore, the proposed equation is tested for wide data sources from both macroscale and nanoscale collisions, and satisfying agreement is achieved, demonstrating the universality of the equation.
Convergent evidence has suggested atypical relationships between brain structure and function in major psychiatric disorders, yet how the abnormal patterns coincide and/or differ across different disorders remains largely unknown. Here, we aim to investigate the common and/or unique dynamic structure–function coupling patterns across major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ).
Methods
We quantified the dynamic structure–function coupling in 452 patients with psychiatric disorders (MDD/BD/SZ = 166/168/118) and 205 unaffected controls at three distinct brain network levels, such as global, meso-, and local levels. We also correlated dynamic structure–function coupling with the topological features of functional networks to examine how the structure–function relationship facilitates brain information communication over time.
Results
The dynamic structure–function coupling is preserved for the three disorders at the global network level. Similar abnormalities in the rich-club organization are found in two distinct functional configuration states at the meso-level and are associated with the disease severity of MDD, BD, and SZ. At the local level, shared and unique alterations are observed in the brain regions involving the visual, cognitive control, and default mode networks. In addition, the relationships between structure–function coupling and the topological features of functional networks are altered in a manner indicative of state specificity.
Conclusions
These findings suggest both transdiagnostic and illness-specific alterations in the dynamic structure–function relationship of large-scale brain networks across MDD, BD, and SZ, providing new insights and potential biomarkers into the neurodevelopmental basis underlying the behavioral and cognitive deficits observed in these disorders.
Increasing evidence shows that maternal hyperglycemia inhibits cardiomyocyte (CM) proliferation and promotes cell apoptosis during fetal heart development, which leads to cardiac dysplasia. Accumulating evidence suggests that the overexpression of miR-21 in CMs has a protective role in cardiac function. Therefore, we investigated whether miR-21 can rescue CM injury caused by high glucose. First, we performed biological function analysis of miR-21-5p overexpression in H9c2 cells treated with high glucose. We found that the proliferation of H9c2 cells treated with high glucose decreased significantly and was rescued after overexpression of miR-21-5p. CCK-8 and EdU incorporation assays were performed to assess cell proliferation. The cell proliferation of the miR-21-5p mimic transfection group was improved compared with that of the NC mimic group (*p < 0.05, miR-21-5p mimics vs. NC mimics) when the proliferation of H9c2 cells was reduced by high glucose (****p < 0.0001, high glucose (HG) vs. normal glucose (NG)). Then, we verified the targeted and negative regulation of miR-21-5p on Rhob using a dual-luciferase activity assay and RT-qPCR, respectively. We further demonstrated that miR-21-5p regulates Rhob to rescue the inhibition of CM proliferation induced by high glucose. The CCK-8 results showed that the cell proliferation of the siRNA-Rhob group was higher than that of the NC mimic group (***p < 0.001) and that of the cotransfection group with Up-Rhob plasmids and miR-21-5p mimics was lower than that of the miR-21-5p mimic group (*p < 0.05). Conclusion: Overexpression of miR-21-5p rescues the inhibition of high glucose-induced CM proliferation through regulation of Rhob.
Fine mapping and discovery of watermelon rind trait candidate genes are of great significance for modern watermelon breeding and development. In this study, we used the high-resolution genetic mapping and genome-wide genetic variation detection technology, combined with genome survey and sequencing technology, to locate and discover the candidate genes for rind traits of star watermelon varieties ‘Su XuanBai’ and ‘SHLX21’. Firstly, we identified a total of eight quantitative trait loci (QTLs) related to watermelon rind traits on chromosome 6. Secondly, a total of 208,240 single nucleotide polymorphisms and 75,345 small Indels (insertions/deletions) were detected in the two parents by high-coverage re-sequencing, respectively. Based on the genetic variation of the two parents and combined with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using the planta database, the QTL region was reduced to 0.02 Mb. Finally, we identified the six potential regulatory factors for watermelon rind traits using real-time quantitative PCR. In conclusion, our results revealed the fine localization of candidate genes for watermelon rind traits and the successful discovery of candidate genes for regulating watermelon rind traits, which is of importance for watermelon rind traits and breeding-improved watermelon varieties.
Fast neutron absorption spectroscopy is widely used in the study of nuclear structure and element analysis. However, due to the traditional neutron source pulse duration being of the order of nanoseconds, it is difficult to obtain a high-resolution absorption spectrum. Thus, we present a method of ultrahigh energy-resolution absorption spectroscopy via a high repetition rate, picosecond duration pulsed neutron source driven by a terawatt laser. The technology of single neutron count is used, which results in easily distinguishing the width of approximately 20 keV at 2 MeV and an asymmetric shape of the neutron absorption peak. The absorption spectroscopy based on a laser neutron source has one order of magnitude higher energy-resolution power than the state-of-the-art traditional neutron sources, which could be of benefit for precisely measuring nuclear structure data.
We develop a high-fidelity multi-physics model and, by using it, study the energy conversion process of a piezohydroelastic flag. Instead of a regular flag with a clamped upstream leading edge, we use an inverted flag so as to make the best of fluid elastic instability for energy harvesting. Moreover, different from many previous studies where a resistor–capacitor (RC) circuit is usually used, we adopt a resistor–inductor–capacitor (RLC) circuit for electricity generation. The influences of several key parameters associated with fluid, structure and electric dynamics are studied. Significantly different response modes are identified, among which the symmetric- and asymmetric-flutter modes are most suitable for sustainable energy harvesting, both emerging with moderate bending stiffness. If only deploying the RC circuit, increasing the resistance makes the flag more stable. By adding an inductor to turn the RC circuit into an RLC one, we observe the occurrence of ‘lock-in’ between the flag frequency and the circuit frequency as first reported on a regular flag by Xia et al. (Phys. Rev. Appl., vol. 3, 2015, 014009). This phenomenon can significantly enhance the energy output, but it only happens when the circuit resistance is sufficiently large. From a derivation based on dynamic mode decomposition analysis, we further identify an optimal condition for maximizing the energy output, which can serve as a guideline to determine whether deploying an inductor can boost the performance, and, if yes, the required inductance. The findings from this study can better guide the design of flow-induced-vibration-based piezoelectric energy harvesters for microelectronic devices.
COVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns.
Methods
Based on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visits before and after the strict Omicron lockdown were included; 85 children were lockdown-free, while 52 and 51 children were under the longer and the shorter durations of strict lockdown, respectively. We tested the association of the lockdown group with the clinical improvement and also the modulation effects of parent/family-related factors on this association by linear regression/mixed-effect models. Within the social brain structures, we examined the voxel-wise interaction between the grey matter volume and the identified modulation effects.
Results
Compared with the lockdown-free group, the ASD children experienced the longer duration of strict lockdown had less clinical improvement (β = 0.49, 95% confidence interval (CI) [0.19–0.79], p = 0.001) and this difference was greatest for social cognition (2.62 [0.94–4.30], p = 0.002). We found that this association was modulated by parental agreeableness in a protective way (−0.11 [−0.17 to −0.05], p = 0.002). This protective effect was enhanced in the ASD children with larger grey matter volumes in the brain's mentalizing network, including the temporal pole, the medial superior frontal gyrus, and the superior temporal gyrus.
Conclusions
This longitudinal neuroimaging cohort study identified that the parental agreeableness interacting with the ASD children's social brain development reduced the negative impact on clinical symptoms during the strict lockdown.
Biochar is increasingly used in crop production as a fertilizer; however, its effects on nutrient cycling and stoichiometry in rice paddy soil–plant systems are unclear. We tested for effects of contrasting rates of biochar on soil and rice plant organ carbon (C), nitrogen (N), and phosphorus (P) concentrations and stoichiometry and soil physicochemical properties in early and late paddies. Overall, biochar reduced soil bulk density by an average of 7.4%, while application at 10, 20, and 40 t ha−1 increased soil C and N concentrations in early paddies by 31.6, 41.3, and 104.2%, respectively, and by 8.0, 5.0, and 21.8%, respectively; in late paddies, there were increases of 23.0, 94.1, and 117.0%, respectively, and 6.7, 15.4, and 18.0%, respectively (P < 0.05). Following biochar application at 10, 20, and 40 t ha−1, soil concentration of P decreased in early paddies by 10.9, 19.0, and 13.9%, respectively, and increased in late paddies by 4.3, 16.4, and 20.1%, respectively. Biochar increased ratios of soil C:N and C:P in early and late paddies (P < 0.05), and there was no effect on concentration and stoichiometry of soil available nutrients. Biochar reduced rice plant organ concentration of N and P in early rice and increased leaf N:P ratios. Despite the biochar application improved nutrient status in plant–soil system, we did not observe a significant increase in yield (P > 0.05). According to the N:P value of leaves between treatments, it was found that biochar alleviated the current situation of N limitation in paddy fields during the mature period and transformed the N limitation of early rice into a joint limitation of N and P. These results show that the addition of biochar to subtropical paddy soils leads to a short-term reduction in soil bulk density and increases in soil C and N concentrations and soil fertility. Thus, biochar applied at optimal rates is likely to improve the sustainability of subtropical paddy rice production.
Varicella vaccination is optional and requires self-payment. On 1 December 2018, Wuxi City launched a free varicella vaccination program for children. This study aimed to evaluate the changes in varicella incidence before and after the implementation of the policy. The data were obtained from official information systems and statistical yearbooks. We divided the period into chargeable (January 2017 to November 2018) and free (December 2018 to December 2021) periods. Interrupt time series analysis was used to conduct a generalised least-squares regression analysis for the two periods. A total of 51,071 varicella cases were reported between January 2017 and December 2021. After the implementation of the policy, there was a statistically significant decrease in the incidence of varicella (β2 = −0.140, P = 0.017), and the slope of the incidence also decreased by 0.012 (P = 0.015). Following policy implementation, the incidence decreased in all age groups, with the largest decline observed among children aged 8–14 years (β2 = −1.109, P = 0.009), followed by children aged ≤7 years (β2 = −0.894, P = 0.013). Our study found a significant reduction in the incidence of varicella in the total population after the introduction of free varicella vaccination in Wuxi City.
The incidence of adolescent depressive disorder is globally skyrocketing in recent decades, albeit the causes and the decision deficits depression incurs has yet to be well-examined. With an instrumental learning task, the aim of the current study is to investigate the extent to which learning behavior deviates from that observed in healthy adolescent controls and track the underlying mechanistic channel for such a deviation.
Methods
We recruited a group of adolescents with major depression and age-matched healthy control subjects to carry out the learning task with either gain or loss outcome and applied a reinforcement learning model that dissociates valence (positive v. negative) of reward prediction error and selection (chosen v. unchosen).
Results
The results demonstrated that adolescent depressive patients performed significantly less well than the control group. Learning rates suggested that the optimistic bias that overall characterizes healthy adolescent subjects was absent for the depressive adolescent patients. Moreover, depressed adolescents exhibited an increased pessimistic bias for the counterfactual outcome. Lastly, individual difference analysis suggested that these observed biases, which significantly deviated from that observed in normal controls, were linked with the severity of depressive symoptoms as measured by HAMD scores.
Conclusions
By leveraging an incentivized instrumental learning task with computational modeling within a reinforcement learning framework, the current study reveals a mechanistic decision-making deficit in adolescent depressive disorder. These findings, which have implications for the identification of behavioral markers in depression, could support the clinical evaluation, including both diagnosis and prognosis of this disorder.
To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ).
Methods
We systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ.
Results
TWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ.
Conclusions
Our findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.