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Background and Hypothesis The gut-brain axis plays important roles in both gastrointestinal diseases (GI diseases) and schizophrenia (SCZ). Moreover, both GI diseases and SCZ exhibit notable abnormalities in brain subcortical volumes. However, the genetic mechanisms underlying the comorbidity of these diseases and the shared alterations in brain subcortical volumes remain unclear. Study Design Using the genome-wide association studies data of SCZ, 14 brain subcortical volumes, and 8 GI diseases, the global polygenic overlap and local genetic correlations were identified, as well as the shared genetic variants among those phenotypes. Furthermore, we conducted multi-trait colocalization analyses to bolster our findings. Functional annotations, cell-type enrichment, and protein-protein interaction (PPI) analyses were carried out to reveal the critical etiology and pathology mechanisms. Study Results The global polygenic overlap and local genetic correlations informed the close relationships between SCZ and both GI diseases and brain subcortical volumes. Moreover, 84 unique lead-shared variants were identified. The associated genes were linked to vital biological processes within the immune system. Additionally, significant correlations were observed with key immune cells and the PPI analysis identified several histone-associated hub genes. These findings highlighted the pivotal roles played by the immune system for both SCZ and GI diseases, along with the shared alterations in brain subcortical volumes. Conclusions These findings revealed the shared genetic architecture contributing to SCZ and GI diseases, as well as their shared alterations in brain subcortical volumes. These insights have substantial implications for the concurrent development of intervention and therapy targets for these diseases. [ABSTRACT FROM AUTHOR]

Aims: Previous studies have indicated that smoking is linked to an increased risk of developing schizophrenia, and that individuals with schizophrenia are more prone to engaging in antisocial behavior. However, the causal effects of smoking behaviors on antisocial behavior and the potential mediating role of schizophrenia remains largely unclear. Methods: In the present study, using the summary data from genome wide association studies of smoking phenotypes (N = 323,386–805,431), schizophrenia (Ncases = 53,386, Ncontrols = 77,258), and antisocial behavior (N = 85,359), we assessed bidirectional causality between smoking phenotypes and schizophrenia by the Mendelian randomization (MR) approach. Using a two‐step MR approach, we further examined whether causal effects of smoking phenotypes/schizophrenia on antisocial behavior were mediated by schizophrenia/smoking phenotypes. Results: The results showed that smoking initiation (SmkInit) and age of smoking initiation (AgeSmk) causally increase the risk of schizophrenia (SmkInit: OR = 2.06, 95% CI = 1.77–2.39, p = 4.36 × 10−21; AgeSmk: OR = 0.32, 95% CI = 0.16–0.62, p = 8.11 × 10−4, Bonferroni corrected). However, there was no causal effect that liability to schizophrenia leads to smoking phenotypes. MR evidence also revealed causal influences of SmkInit and the amount smoked (CigDay) on antisocial behavior (SmkInit: OR = 1.28, 95% CI = 1.17–1.41, p = 2.53 × 10−7; CigDay: OR = 1.16, 95% CI = 1.06–1.27, p = 1.60 × 10−3, Bonferroni corrected). Furthermore, the mediation analysis indicated that the relationship between SmkInit and antisocial behavior was partly mediated by schizophrenia (mediated proportion = 6.92%, 95% CI = 0.004–0.03, p = 9.66 × 10−3). Conclusions: These results provide compelling evidence for taking smoking interventions as a prevention strategy for schizophrenia and its related antisocial behavior. [ABSTRACT FROM AUTHOR]

Neuroimaging studies have demonstrated that migraine is accompanied by spontaneous brain activity alterations in specific regions. However, these findings are inconsistent, thus hindering our understanding of the potential neuropathology. Hence, we performed a quantitative whole‐brain meta‐analysis of relevant resting‐state functional imaging studies to identify brain regions consistently involved in migraine. A systematic search of studies that investigated the differences in spontaneous brain activity patterns between migraineurs and healthy controls up to April 2022 was conducted. We then performed a whole‐brain voxel‐wise meta‐analysis using the anisotropic effect size version of seed‐based d mapping software. Complementary analyses including jackknife sensitivity analysis, heterogeneity test, publication bias test, subgroup analysis, and meta‐regression analysis were conducted as well. In total, 24 studies that reported 31 datasets were finally eligible for our meta‐analysis, including 748 patients and 690 controls. In contrast to healthy controls, migraineurs demonstrated consistent and robust decreased spontaneous brain activity in the angular gyrus, visual cortex, and cerebellum, while increased activity in the caudate, thalamus, pons, and prefrontal cortex. Results were robust and highly replicable in the following jackknife sensitivity analysis and subgroup analysis. Meta‐regression analyses revealed that a higher visual analog scale score in the patient sample was associated with increased spontaneous brain activity in the left thalamus. These findings provided not only a comprehensive overview of spontaneous brain activity patterns impairments, but also useful insights into the pathophysiology of dysfunction in migraine. [ABSTRACT FROM AUTHOR]