Genes Brain and Behavior最新文献

{"title":"Multimodal Neuroimaging and Behavioral Characterization of Aged Female APOE4 Knock-In Rats Reveals a Preclinical Alzheimer's Disease Phenotype","authors":"Noah J. Cavallaro,&nbsp;Ashwath Maheswari,&nbsp;Tochi Chukwuemeka,&nbsp;Allen Koganov,&nbsp;Nithiyashree Sundararaj,&nbsp;Sydney D'Argenio,&nbsp;Harper Stotland,&nbsp;Deena Weiss,&nbsp;Gregorio Botelho,&nbsp;Praveen P. Kulkarni,&nbsp;Craig F. Ferris","doi":"10.1111/gbb.70076","DOIUrl":"10.1111/gbb.70076","url":null,"abstract":"<p>The apolipoprotein E ε4 allele (APOE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD) and confers disproportionate risk in women, particularly after reproductive senescence. The brain changes preceding overt neurodegeneration in APOE4 carriers remain incompletely characterized. We conducted neuroimaging and behavioral studies in aged (18-month) female APOE4 humanized knock-in rats and APOE3 controls. Regional brain volumes across 197 areas were quantified by voxel-based morphometry (VBM); white and gray matter microstructure by diffusion tensor imaging (DTI), yielding fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Spatial memory was assessed with the Barnes maze and motor coordination with the beam walk. APOE4 rats showed significantly larger regional brain volumes than APOE3 controls. DTI revealed increased FA in the thalamus, brainstem, and white matter tracts, and reduced FA in the sensorimotor cortex. Across most regions elevated FA was accompanied by reduced ADC, an inverse relationship consistent with cytotoxic edema. Behaviorally, APOE4 rats were significantly impaired on the Barnes maze. Aged female APOE4 knock-in rats exhibit a preclinical AD phenotype: widespread volumetric enlargement across white matter, sensorimotor, and limbic circuits, with microstructural alterations (elevated FA in brainstem, thalamus, and white matter; reduced FA in sensorimotor cortex). This mirrors the imaging and cognitive profile of cognitively normal human APOE4 carriers in preclinical AD and validates the model as a translationally relevant platform for investigating early APOE4-driven pathophysiology and testing preventive interventions.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149247274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Serotonin Transporter Genotype and (Un)Predictable Maternal Separation on Affective, Cognitive, and Social Behaviors in Female Rats","authors":"Danielle J. Houwing,&nbsp;Mayerli A. Prado-Rivera,&nbsp;Jenny Borkent,&nbsp;Marrit Gerbrandy,&nbsp;Chantal Arling,&nbsp;Jocelien D. A. Olivier","doi":"10.1111/gbb.70069","DOIUrl":"10.1111/gbb.70069","url":null,"abstract":"<p>Serotonin transporter (SERT) variation is linked to depression risk after stress, conferring an increased risk to SERT-linked polymorphic region (5-HTTLPR) short-allele carriers, who show heightened sensitivity to cumulative stress and childhood maltreatment. To elucidate the neurobiological mechanisms underlying SERT × early-life adversity interactions, animal models capturing this genetic vulnerability are of translational relevance. We evaluated four maternal separation (MS) paradigms to determine how different forms of early-life stress influence adult behavior in female SERT-deficient rats, given the higher prevalence of depression in women and the limited translational value of male-only preclinical findings. We applied several behavioral tests to wildtype (SERT^+/+), heterozygous (SERT^+/−), and homozygous (SERT^−/−) knockout females exposed to MS: predictable 3 h/day (MS180) or 6 h/day (MS360), unpredictable 3 h/day (MSU180), or unpredictable 3 h/day plus unpredictable maternal stress (MSUS180). Controls were 15-min handled. SERT^−/− females exhibited higher anxiety-like responses, passive stress coping, and increased social exploration. MS180 and MS360 induced some anxiety-like behaviors, while MS360 increased hedonic responding. Females responded differently to MS depending on their SERT genotype. First, some anxious behaviors of SERT^−/− females were attenuated when exposed to unpredictable MS (MSU180 and MSUS180). Second, MSU180 reduced object recognition in SERT^−/− females, while enhancing it in SERT^+/− females. Third, SERT^+/− females exhibited less passive stress coping when exposed to MS360 than all other groups. Neither predictable nor unpredictable MS exposure increased vulnerability to depressive-related behaviors in SERT-deficient females. Variations in SERT expression may confer some beneficial effects in response to MS, depending on the specific genotype and behavioral domain evaluated.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Cell Models of Specific Reading Disabilities: Identification of Cellular and Transcriptome Alterations","authors":"Cathy L. Barr,&nbsp;Karen G. Wigg,&nbsp;Yu Feng,&nbsp;Kirsten Blokland,&nbsp;Margaret Wilkinson,&nbsp;Elizabeth N. Kerr,&nbsp;Sharon L. Guger,&nbsp;Maureen W. Lovett,&nbsp;Lisa J. Strug,&nbsp;Ruth Oefner,&nbsp;Simone Benassi,&nbsp;Fred H. Gage,&nbsp;Maria C. Marchetto","doi":"10.1111/gbb.70071","DOIUrl":"10.1111/gbb.70071","url":null,"abstract":"<p>Based on post-mortem studies, a long-standing hypothesis on the biological bases of specific reading disabilities (RD) has been that alterations in neuronal migration alter language neural circuits. However, there are questions concerning the original studies (small sample size, comorbidities). Further, this idea has not been strongly supported by current genetic studies. In this study, we test altered neural cell phenotypes using cells derived from two pairs of siblings strongly discordant for reading—probands with severe RD and their strong-reader siblings. We observed significant differences in neurosphere outgrowth between the neural precursor cells (NPCs) from the probands compared to their strong-reader siblings. Transcriptome analyses of adherent NPCs and neurons derived from the NPCs identified genes differentially expressed between the probands and siblings, including genes previously identified in neurodevelopmental disorders. Of note was the overexpression of the hormone <i>IGF1</i> and the transcription factor <i>OTX2</i>, responsible for the opening and closing of critical windows in development and predicted to be involved in critical windows for language acquisition. Our results support altered transcriptome and cellular phenotypes in RD neural cells and suggest possible molecular mechanisms underlying the changes.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reln Haploinsufficiency Enhances Fentanyl-Induced Locomotion and Dorsal Striatal Activity Without Affecting Opioid Reinforcement and Relapse-Like Behavior","authors":"Carl Litif,&nbsp;Avraham M. Libster,&nbsp;Shane Desfor,&nbsp;Tanieng Huang,&nbsp;Leanne Liaw,&nbsp;Annika Cheng,&nbsp;Francesca Telese","doi":"10.1111/gbb.70072","DOIUrl":"10.1111/gbb.70072","url":null,"abstract":"<p>The <i>Reln</i> gene encodes the extracellular glycoprotein Reelin that regulates synaptic plasticity and activity-dependent gene expression with implication in several neuropsychiatric disorders, including substance use disorder. Although reduction of <i>Reln</i> expression has been associated with altered responses to psychostimulants and cannabinoids, its role in opioid-evoked behaviors has not been investigated. Here, we tested whether <i>Reln</i> haploinsufficiency alters behavioral and molecular responses to the synthetic opioid fentanyl. Heterozygous Reeler (<i>Reln</i>+/−) mice and wild-type littermates were assessed using complementary contingent and non-contingent models of fentanyl exposure, including multi-phase fentanyl intravenous self-administration paradigm, conditioned place preference paradigm, locomotor assays, and dorsal striatal immediate early gene expression. <i>Reln</i> haploinsufficiency did not alter acquisition, extinction, or cue-induced fentanyl seeking during self-administration, indicating stable opioid reinforcement and relapse-like behavior. Following acute, passive fentanyl exposure, <i>Reln</i>+/− mice exhibited enhanced fentanyl-induced locomotion and Fos immunoreactivity in the dorsal striatum, while fentanyl conditioned place preference remained unchanged. Together, these findings demonstrate that <i>Reln</i> haploinsufficiency does not modify opioid reinforcement or cue-driven drug seeking but enhances acute drug-evoked neuronal activation in the dorsal striatum. These results identify <i>Reln</i> as a modulatory factor in opioid-responsive neural circuits rather than in the associative learning processes underlying opioid reinforcement.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrated Analysis of Manganese Metabolism-Related Genes and Their Association With Biomarkers, Immune Infiltration, and Clinical Subtypes in Alzheimer's Disease","authors":"Shengnan Shu,&nbsp;Jiahao Hu,&nbsp;Shanshan Hu,&nbsp;Yefeng Yao","doi":"10.1111/gbb.70059","DOIUrl":"10.1111/gbb.70059","url":null,"abstract":"<p>Alzheimer's disease (AD), a neurodegenerative condition marked by amyloid-beta plaques and tau protein neurofibrillary tangles, progresses against a backdrop of essential biological processes. Manganese, an indispensable trace element for vital functions including energy metabolism and antioxidant defense, is integral to neurological health. Its precise metabolic role throughout the course of AD pathogenesis is not fully elucidated. Four essential manganese metabolism-related genes were identified as diagnostic markers through a multi-omic framework. This approach integrated Weighted Gene Co-Expression Network Analysis with machine learning ensembles (Least Absolute Shrinkage and Selection Operator/Random Forest/Extreme Gradient Boosting), followed by rigorous testing in an independent dataset. Beyond identification, we utilized CIBERSORT and ssGSEA to characterize immune infiltration and leveraged GSEA/GO/KEGG for pathway elucidation. Finally, AD patients were stratified into molecular subgroups based on these hub genes, and their underlying regulatory networks involving miRNAs and transcription factors were reconstructed. An integrated bioinformatics framework identified 12 differentially expressed genes related to manganese metabolism in AD. Machine-learning–based feature selection further pinpointed four key diagnostic biomarkers (TSPO, PTBP1, GLO1, and ACACB) with high discriminative power (AUC: 0.831–0.905). Immune infiltration analysis revealed substantial immune remodeling in AD, including an elevation of naïve B cells. Moreover, AD samples were classified into two molecular subtypes displaying distinct immune and metabolic characteristics, and regulatory miRNA/TF interaction networks were constructed for the core genes. Our results shed new light on the molecular mechanisms underlying AD and support future efforts toward early diagnosis and personalized therapeutic interventions based on molecular subtypes.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Pre-Trauma Corticosterone Attenuates Trauma Memory Formation and Alters Gene Expression in Glucocorticoid Signalling Pathways","authors":"Gia Kutelia,&nbsp;Zurab Kuchukashvili,&nbsp;Rusiko Ansiani,&nbsp;Roza Bukia,&nbsp;Manana Chikovani,&nbsp;Butsiko Chkhartishvili,&nbsp;Nanuli Doreulee","doi":"10.1111/gbb.70067","DOIUrl":"https://doi.org/10.1111/gbb.70067","url":null,"abstract":"<p>Glucocorticoid signalling plays a central role in the processing of traumatic memories and contributes to adaptive and pathological responses to stress, with dysregulation frequently reported in trauma-related conditions such as post-traumatic stress disorder (PTSD). A key stage in trauma memory formation is the early consolidation window, during which aversive experiences are stabilised into long-term memory through protein synthesis and activity-dependent gene expression. To investigate how glucocorticoid levels during trauma exposure shape this process, we examined the behavioural and molecular consequences of acute and chronic corticosterone elevation, the rodent analogue of cortisol. Adult male mice received either repeated corticosterone injections for 5 days prior to fear conditioning (FC) or vehicle injections for 5 days followed by a single corticosterone injection immediately before FC. Two hours after FC, we quantified expression of genes encoding mineralocorticoid receptors (<i>Nr3c2</i>, MR), glucocorticoid receptors (<i>Nr3c1</i>, GR), and FK506-binding protein 5 (<i>Fkbp5</i>) in the amygdala, hippocampus, and anterior cingulate cortex (ACC). Trauma memory was assessed 24 h later by measuring freezing and exploratory behaviour to conditioned cues in separate experimental cohorts. Chronic corticosterone exposure was associated with attenuated conditioning-related behavioural responses, whereas acute corticosterone did not alter these responses. These effects were accompanied by region-specific alterations in glucocorticoid-signalling gene expression, most notably coordinated regulation of hippocampal and ACC <i>Nr3c2</i> following FC. We propose that this regional <i>Nr3c2</i> transcriptional signature represents an early molecular adaptation to prolonged glucocorticoid exposure that may alter hippocampal–prefrontal communication during trauma-memory formation.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148903952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive Deficits in Female GPR158 Knockout Mice Revealed by Automated Home-Cage Testing","authors":"Alyson P. Blount,&nbsp;Shradha V. Darira,&nbsp;Emmanuelle B. Palmieri,&nbsp;Laurie P. Sutton","doi":"10.1111/gbb.70066","DOIUrl":"https://doi.org/10.1111/gbb.70066","url":null,"abstract":"<p>GPR158 is a G protein coupled receptor (GPCR) that is abundantly expressed in the brain and has been shown to organize synaptic architecture and regulate synaptic function. Previous studies have demonstrated a role for GPR158 in hippocampal-dependent learning and stress-related affective behaviors yet its contribution to cognitive function under naturalistic, low-stress conditions remains unclear. Here, we investigated the role of GPR158 in spatial learning, cognitive flexibility, and working memory using both traditional and automated home-cage paradigms. The use of automated, socially enriched testing paradigms minimizes stress-related confounds and allows us to discover the naturalistic roles of GPR158 in cognition and behavior. Using the IntelliCage to test spatial learning and working memory in a social enriched environment, we found that female GPR158 knockout mice exhibited deficits in spatial learning but showed intact working memory. Consistent with these findings, spatial impairments were also observed in the Barnes Maze, where female GPR158 KO mice showed pronounced deficits in spatial strategy acquisition, increased latency, reduced time spent in the reward area, and impaired performance during the probe trial. Male GPR158 knockout mice showed no significant difference in either spatial learning or working memory compared to their wild-type littermates in the IntelliCage, whereas in the Barnes Maze knockout mice showed mild impairment in spatial strategy acquisition. These findings reveal a profound impairment with female GPR158 knockout mice in hippocampal-dependent cognition and highlight the importance of low-stress, ethologically testing environments.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic Behavioural Effects of Genetic Deletion of the Vesicular Glutamate Transporter 3 in 5-Hydroxytryptamine Neurons","authors":"L. Sophie Gullino,&nbsp;Nida Chabbah,&nbsp;Spatika Jayaram,&nbsp;Raquel Pinacho,&nbsp;Salah El Mestikawy,&nbsp;Stéphanie Daumas,&nbsp;David M. Bannerman,&nbsp;Trevor Sharp","doi":"10.1111/gbb.70063","DOIUrl":"10.1111/gbb.70063","url":null,"abstract":"<p>A major subpopulation of 5-hydroxytryptamine (5-HT) neurons expresses the vesicular glutamate transporter 3 (VGLUT3) allowing the co-release of glutamate. Previous evidence has implicated VGLUT3 in 5-HT neurons in mechanisms of anxiety and reward. Here we examined mice with a genetic loss of VGLUT3 targeted to 5-HT neurons (VGLUT3 cKO^5-HT) and littermate controls in a battery of behavioural tests, including paradigms assessing levels of anxiety and learning with appetitive rewards. Compared to littermate controls, VGLUT3 cKO^5-HT mice displayed no evidence of altered anxiety-like behaviour in the elevated plus maze, light/dark box, marble burying and social interaction tests. However, VGLUT3 cKO^5-HT mice showed reduced preference for low (but not high) sucrose-containing solution and reduced correct responses in an appetitively motivated spatial reference memory task. Similarly, in an appetitively motivated operant task, VGLUT3 cKO^5-HT mice displayed evidence of reduced responding to cues associated with reward. These effects appeared specific in that VGLUT3 cKO^5-HT mice did not differ from controls in terms of home cage food consumption, performance in a spatial novelty preference test, as well as contextual and cued fear memory tests. These findings support a role for VGLUT3 in 5-HT neurons in some aspects of learning, here in association with learning for reward, although not anxiety-like behaviour.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148594449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological and Behavioural Characterisation of a Novel Steroid Sulfatase-Deficient Mouse","authors":"Trevor Humby,&nbsp;Freya R. Shepherd,&nbsp;Talia Elgie,&nbsp;Libby Anderson-Watkins,&nbsp;Lucy I. Beevors,&nbsp;Angela E. Taylor,&nbsp;Paul A. Foster,&nbsp;William Davies","doi":"10.1111/gbb.70061","DOIUrl":"10.1111/gbb.70061","url":null,"abstract":"<p>Steroid sulfatase (STS) cleaves sulphate groups from steroid hormones. In humans, STS deficiency is associated with X-linked ichthyosis, an increased predisposition to neurodevelopmental and mood conditions (including Attention Deficit Hyperactivity Disorder, autism, depression and anxiety), and cardiac arrhythmia risk. Until recently, no single-gene ‘knockout’ mammalian model existed; previous work in such a model is limited to skin phenotypes. We generated a novel C57BL/6J mouse model with a deletion in exon 2 of <i>Sts</i>. We examined gene expression and enzyme activity in liver and brain samples of homozygous mice, and assessed the breeding performance and health of male and female deletion-carriers. Subsequently, we compared performance across a range of behavioural paradigms in wildtype and homozygous male and female mice: elevated plus maze, open field, rotarod, spontaneous alternation, and acoustic startle/prepulse inhibition. We also investigated serum steroid hormone levels by liquid chromatography-mass spectrometry and measured heart weights and two morphological indices (bodyweight/tibia length) <i>post mortem</i>. Homozygous mice almost completely lacked STS expression/activity. Genetically-altered mice exhibited grossly-normal breeding performance, health, and endocrinology. Homozygous mice were more active and had higher normalised heart weights than wildtype mice. We also found significant genotype × sex interactions on bodyweight and on two behavioural measures (potentially reflecting lower anxiety in homozygous males and heightened anxiety in homozygous females). The ‘<i>Sts</i>-deletion’ mouse represents an experimentally-tractable model in which to identify and characterise phenotypes associated with STS deficiency. The mechanistic basis of the associations described here requires further investigation, and whether these translate to humans remains to be tested.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiancestry and Multitrait GWAS Meta-Analysis on Schizophrenia With a Sample of 322,321 Unveils Genetic Links to Chronic Lung Diseases","authors":"Abudusalamu Ayoufu,&nbsp;Ayinigeer Abulimiti,&nbsp;Wusimanjiang Aierken,&nbsp;ZhouBin Wei,&nbsp;XueCheng Wang,&nbsp;HaiFeng Wang,&nbsp;Liang Zhao","doi":"10.1111/gbb.70062","DOIUrl":"10.1111/gbb.70062","url":null,"abstract":"<p>Schizophrenia (SCZ) is a highly heritable psychiatric disorder, yet its genetic links with chronic pulmonary diseases remain poorly defined. Such links may reflect shared biological pathways and could create opportunities for cross-disorder risk prediction and therapeutic repurposing. Here we applied a multiancestry, multitrait GWAS framework to SCZ and chronic pulmonary disease datasets. The analysis included 322,321 participants of European and East Asian ancestry from the Psychiatric Genomics Consortium, FinnGen, and 23andMe. We identified 16 previously unreported genetic variants associated with schizophrenia across ancestries. Transcriptome-wide association analysis and machine learning prioritization highlighted candidate genes, including WBP1L and CNNM2, that may contribute to schizophrenia biology. Gene-expression-based drug repurposing further nominated potential therapeutic opportunities shared across psychiatric and pulmonary traits. These findings indicate that schizophrenia and chronic pulmonary diseases share part of their inherited architecture, supporting integrated genetic models for comorbidity, risk stratification, and therapeutic discovery.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}