Genes Brain and Behavior最新文献

{"title":"Repeated Stress Escalates Aggression and Activity in Fronto-Limbic Regions in Cntnap2−/− Mice","authors":"Caroline H. Hertweck,&nbsp;Chase A. Carter,&nbsp;Sarah S. McDaniel,&nbsp;Pierre Llorach,&nbsp;Hayleigh E. Tilton,&nbsp;Anish Kodali,&nbsp;Daniel J. Christoffel,&nbsp;Jessica J. Walsh","doi":"10.1111/gbb.70048","DOIUrl":"10.1111/gbb.70048","url":null,"abstract":"<p>Autism spectrum disorder (ASD) is characterized by social impairments and stereotyped behavior, with some individuals exhibiting heightened aggression in response to stress. This stress induced aggression (SIA) can severely impact quality of life, yet its underlying neural mechanisms remain poorly understood. Here, we investigated the behavioral phenotypes and neural activity that result as a consequence of stress in <i>Cntnap2</i>^{<i>−/−</i>}<i>:TRAP2</i>^<i>+/−</i><i>:Ai14</i>^<i>+/−</i> mice. Deletion of the <i>CNTNAP2</i> gene leads to a highly penetrant syndromic form of ASD, and the targeted recombination in active populations (TRAP) system allows for permanent access to neuronal populations activated during a specific experience, such as stress and aggression. We implemented a behavioral paradigm consisting of a baseline resident intruder assay, with either a single day or four consecutive days of restraint stress, followed by a posttest resident intruder assay in <i>Cntnap2</i>^{<i>−/−</i>}<i>:TRAP2</i>^<i>+/−</i><i>:Ai14</i>^<i>+/−</i> and control mice. While a single day of restraint stress failed to induce changes in aggressive behavior in either genotype, 4 days of restraint stress significantly escalated aggression and reduced latency to attack selectively in <i>Cntnap2</i>^{<i>−/−</i>} mice. Using TRAP-based labeling, we observed increased neuronal activity in the lateral septum, lateral habenula, lateral hypothalamus, nucleus accumbens, and prelimbic cortex of <i>Cntnap2</i>^{<i>−/−</i>} mice. Interestingly, time aggressive and aggressive events were positively correlated with activity in the lateral septum, lateral habenula, and infralimbic cortex. These findings suggest that repeated stress engages specific fronto-striatal and limbic regions in <i>Cntnap2</i>^{<i>−/−</i>} mice and provide insight into the neural substrates of maladaptive SIA, offering a foundation for targeted therapeutic strategies.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445560","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":"Calorie Restriction Effects on Aging, Learning Performance, and Transcription in Aged Aplysia californica","authors":"Eric C. Randolph,&nbsp;Lynne A. Fieber","doi":"10.1111/gbb.70046","DOIUrl":"10.1111/gbb.70046","url":null,"abstract":"<p>Along with increasing an animal's lifespan, calorie restriction (CR) is shown to improve an animal's cognition. To elucidate the molecular differences that accompany CR that may benefit cognition, sibling <i>Aplysia californica</i> were reared on either an ad-lib (AL) or CR diet. Siblings from each diet were trained in two behaviors, learning food is inedible (LFI) and habituation of the tail withdrawal reflex (TWR), at two time points along their lifespans: younger animals at training time 1 (TT1) and aged siblings at training time 2 (TT2). In analysis by diet, TT2 CR animals' learning performance was on par with their TT1 CR siblings in both paradigms, illustrating a maintenance of cognition in age. Meanwhile, TT2 AL animals performed worse than TT1 AL siblings in habituation but better in LFI, illustrating the lack of cognitive maintenance in age. RNA sequencing was performed on part of the buccal ganglia that houses many of the neurons involved in LFI. Gene expression results implied morphological changes occurring within the motor and interneurons of the buccal ganglia after learning in LFI. These neurons showed enrichment of <i>protein kinase C binding</i> (GO:0005080), <i>cadherin binding</i> (GO:0045296), and <i>microtubule severing ATPase activity</i> (GO:0008568) as well as <i>neuroactive ligand-receptor interaction</i> (ko04080) and <i>valine, leucine and isoleucine biosynthesis</i> (ko00290) all of which have been implicated to assist in memory consolidation and reconsolidation.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12937505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147291678","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":"Abnormal Hearing Phenotypes in “Ignorome” Knockout Mice as Predictors of Cognitive Dysfunction","authors":"Sergio Vicencio-Jimenez,&nbsp;Micheal L. Dent,&nbsp;Amanda M. Lauer","doi":"10.1111/gbb.70045","DOIUrl":"10.1111/gbb.70045","url":null,"abstract":"<p>Alzheimer's disease and related dementias affect over 55 million people worldwide and are one of the most pressing public health challenges. Age-related hearing loss has emerged as a strong predictor of Alzheimer's disease and related dementias risk, raising the possibility that auditory dysfunction may serve as an early biomarker. While the causal nature of the relationship remains uncertain, treating hearing loss, or addressing a shared underlying mechanism, may improve quality of life and slow symptom progression in at-risk individuals. Current animal models of Alzheimer's disease largely focus on rare familial mutations, limiting their ability to capture the genetic and phenotypic heterogeneity of late-onset disease. To explore broader genetic contributions and potential links between hearing and cognition, we leveraged data from the International Mouse Phenotyping Consortium, a large-scale resource that provides standardized phenotyping across thousands of knockout mouse lines. Genes with abnormal auditory phenotypes were more likely to display behavioral abnormalities compared to genes without auditory involvement. Although other sensory modalities such as vision also showed associations with behavioral traits, the links to auditory dysfunction were stronger. Furthermore, higher auditory brainstem response thresholds correlated with the number of behavioral abnormalities across genotypes. Gene Ontology enrichment analyses of genes with auditory and behavioral phenotypes revealed distinct biological processes potentially linking sensory decline and cognitive vulnerability. These findings highlight candidate genes and molecular pathways connecting age-related hearing loss and Alzheimer's disease and related dementias, provide alternative genetic models that better reflect disease complexity, and suggest new avenues for early detection and intervention.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286184","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":"Methylation Status of the DAT1 Dopamine Transporter Gene in Individuals With Cannabis Use Disorder: Associations With Personality Traits","authors":"Aleksandra Suchanecka,&nbsp;Remigiusz Recław,&nbsp;Krzysztof Chmielowiec,&nbsp;Jolanta Chmielowiec,&nbsp;Jolanta Masiak,&nbsp;Anna Grzywacz","doi":"10.1111/gbb.70040","DOIUrl":"10.1111/gbb.70040","url":null,"abstract":"<p>Cannabis use is a growing public health concern due to its neuropsychiatric consequences and potential epigenetic effects. This study investigated the methylation status of the <i>DAT1</i> dopamine transporter gene in individuals with cannabis use disorder (CUD) and examined associations with personality traits. A total of 490 male participants (212 with CUD and 278 controls) were assessed using the NEO Five-Factor Inventory (NEO-FFI) and the State–Trait Anxiety Inventory (STAI). DNA methylation levels at 33 CpG sites within the <i>DAT1</i> promoter region were quantified through methylation-specific PCR and sequencing. Although no significant group differences were found in overall methylation levels, logistic regression revealed significant associations between methylation status and personality dimensions. CUD was linked to higher neuroticism and openness, lower agreeableness and conscientiousness, and elevated anxiety scores. Importantly, reduced <i>DAT1</i> methylation was a significant predictor of CUD. These findings underscore the interplay between personality, gene regulation, and addiction, supporting a role for epigenetic mechanisms in the development and maintenance of substance use disorders. Future research should explore site-specific CpG alterations and their longitudinal impact on neurobehavioral outcomes.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769780","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":"The Drosophila SIFamide Receptor Regulates Sleep and Feeding in a Time-Of-Day Specific Manner","authors":"Anayatzi Velazquez,&nbsp;Madelyn R. Cusick,&nbsp;Siddarth De,&nbsp;Andi A. Beaudouin,&nbsp;Ariel Stepankovskaya,&nbsp;Justina A. Tidaback,&nbsp;Oleksandra Tsibere,&nbsp;Daniel J. Cavanaugh","doi":"10.1111/gbb.70043","DOIUrl":"10.1111/gbb.70043","url":null,"abstract":"<p>To optimize health, organisms must coordinate energy intake and expenditure and apportion related behaviors to appropriate times of day. In the fruit fly, <i>Drosophila melanogaster</i>, the SIFamide (SIFa) neuropeptide impacts multiple behavioral outputs important for energy regulation, including reproductive activity, sleep, and feeding. SIFa-expressing neurons receive convergent inputs from circadian and homeostatic brain regions and extend elaborate projections throughout the central nervous system. Consistent with this distribution pattern, the SIFa receptor (SIFaR) is widely expressed in the brain and ventral nerve cord, providing the anatomical substrate for SIFa signaling to influence a broad range of neuronal functions. To further explore the pleiotropic role of SIFa signaling in behavioral control, we have assessed survival, locomotor activity, sleep, and feeding in <i>SIFaR</i> mutant flies, as well as in flies with RNA interference-induced reduction of <i>SIFaR</i> expression. We find that loss of SIFaR has a complex effect on fly survival that is background- and allele-specific. However, outcrossed <i>SIFaR</i> mutant flies are viable, enabling monitoring of adult behavior. These flies exhibit elevated locomotor activity, reduced sleep, and increased feeding at specific times of day. We also find that <i>SIFaR</i> mutations drastically decrease starvation resistance. These results suggest a prominent role for SIFaR in integrating homeostatic and circadian information to coordinate the magnitude and timing of energy balance-related behaviors.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716322","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":"Sex-Specific, Intermediate Behavioral Phenotypes in Heterozygous Dopamine Transporter Mutant DAT T356M Mice","authors":"Emma Harris,&nbsp;Krista C. Paffenroth,&nbsp;Adriana A. Tienda,&nbsp;Fiona E. Harrison,&nbsp;Mark T. Wallace","doi":"10.1111/gbb.70041","DOIUrl":"10.1111/gbb.70041","url":null,"abstract":"<p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with both genetic and environmental contributions. Previous work identified a de novo mutation in the dopamine transporter (DAT T356M) in an autism proband that results in profound behavioral changes when expressed homozygously in mice. Since complex human genetics are more likely to be present as heterozygous (single allele) mutations, we characterized mice that were heterozygous for the mutation. Both male and female DAT T356M^+/− mice exhibited hyperactivity but normal habituation to novel environments. The difference in hyperactivity compared to wild-type littermates was dramatically smaller than previously reported in homozygous animals. Other behavioral alterations were sex-specific, with only male heterozygous mice exhibiting greater repetitive behaviors and impaired spatial learning in the Barnes maze. Sensorimotor gating measured by prepulse inhibition of the startle response was largely unchanged in both sexes. Motor performance on the rotarod showed opposing effects, with male heterozygotes showing decreased latency to fall while females demonstrated increased latency (i.e., enhanced performance). These findings suggest that even a single copy of the DAT T356M variant can impact behavior in a sex-specific manner. The identification of intermediate phenotypes makes these mice an appropriate model for future studies examining how environmental factors might interact with genetic susceptibility to influence autism-relevant behaviors, particularly in the context of dopaminergic dysfunction.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12640684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589965","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":"Shared Genetic Links Between Birth Weight and Developmental-Behavioral Disorders","authors":"Rongyue Sun,&nbsp;Guosheng Yu,&nbsp;Yanzhao Luo,&nbsp;Shikang Fan,&nbsp;Junhui Yuan","doi":"10.1111/gbb.70042","DOIUrl":"10.1111/gbb.70042","url":null,"abstract":"<p>While observational studies have linked birth weight to developmental-behavioral disorders, establishing genetic correlations and causal relationships remains challenging due to potential confounding factors. In this study, we assessed genetic correlations between birth weight and developmental-behavioral disorders using linkage disequilibrium score regression (LDSC), identified pleiotropic loci and genes through Pleiotropy Analysis under Composite Null Hypothesis (PLACO), and investigated causal relationships via Mendelian randomization (MR) analysis. The results revealed significant negative genetic correlations between ADHD and birth weight (fetal: <i>r</i>_g = −0.087, 95% CI −0.134 to −0.040; maternal: <i>r</i>_g = −0.088, 95% CI −0.139 to −0.0337; maternal effect: <i>r</i>_g = −0.107, 95% CI −0.183 to −0.030). We identified 41 pleiotropic genes enriched in cardiovascular, brain, and liver tissues, and 122 pleiotropic loci through eQTL integration. However, MR analysis showed no causal associations between birth weight and developmental behavioral disorders. These analyses establish both shared genetic etiology and biological pleiotropy underlying birth weight and developmental-behavioral disorder associations.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12640763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588431","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":"Spatiotemporal Patterns of Gene Expression Associated With Mating Stimuli in the Brain of Female Guppies","authors":"Amaury Bittar,&nbsp;Catalina Botia,&nbsp;Santiago Martínez,&nbsp;Daniela Bernal,&nbsp;Nicolas Aparicio,&nbsp;Luis Felipe Giraldo,&nbsp;Verónica Akle,&nbsp;Natasha I. Bloch","doi":"10.1111/gbb.70035","DOIUrl":"https://doi.org/10.1111/gbb.70035","url":null,"abstract":"<p>Investigating the spatiotemporal patterns of gene expression in the brain is a critical step toward unraveling the molecular mechanisms underlying social behavior. While significant progress has been made in identifying neurogenomic states associated with diverse social contexts and their biological pathways, genomic studies often yield hundreds of candidate genes. This necessitates pinpointing key genes that drive behavior for more targeted research. In this study, we examine how the spatiotemporal expression of selected candidate genes varies between mating and social contexts. Building on insights from previous transcriptomic analyses, we identified promising gene candidates and examined their expression patterns in the female guppy brain (<i>Poecilia reticulata</i>). We evaluated these patterns within the brain's social decision-making network at 10 and 30 min post-exposure to either a mating or social stimulus. Genes such as <i>gria1a</i>, <i>thap6</i>, <i>gria2</i>, and <i>agap3</i> exhibited the most pronounced differences in expression between mating and social contexts, suggesting their potential roles in regulating mating behavior. Employing a novel hierarchical coexpression network analysis, we captured the intricate gene expression changes underlying behavior. This approach allowed us to visualize distinct patterns of brain activity, revealing that the response to mating stimuli was localized to anterior nuclei, whereas the response to social stimuli was more evenly distributed across the social decision-making network. Additionally, we observed greater variability in gene expression between social and mating contexts at the 10-min time point.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145398970","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":"Cul3 Postnatal Homozygous Deletion in Forebrain Results in Behavioral Differences","authors":"Prathibha Sekar,&nbsp;Qiang-qiang Xia,&nbsp;Alex C. Stokes,&nbsp;Feiyu Quan,&nbsp;Jeffrey D. Singer,&nbsp;Craig M. Powell","doi":"10.1111/gbb.70039","DOIUrl":"https://doi.org/10.1111/gbb.70039","url":null,"abstract":"<p>Large-scale human genetic studies implicate multiple genes that regulate protein ubiquitination in autism spectrum disorder (ASD). De novo loss-of-function mutations in the gene <i>CULLIN3 (CUL3)</i> are implicated in autism and intellectual disability (ID). CUL3 is an essential component of an E3 ubiquitin ligase complex required for ubiquitination of substrates, often a signal for proteasomal degradation. Homozygous deletion of <i>Cul3</i> is embryonically lethal. Recent studies show heterozygous deletion of <i>Cul3</i> results in phenotypes with some face validity for autism in constitutive and conditional <i>Cul3</i> heterozygotes. To understand the function of <i>Cul3</i> in late postnatal development and function in the brain, we crossed mice expressing Cre-recombinase under the control of the <i>CaMKIIα</i> promoter with conditional (floxed) <i>Cul3</i> mice that resulted in viable homozygotes. In this study, we demonstrate that delayed postnatal deletion of <i>Cul3</i> in predominantly forebrain excitatory neurons leads to robust behavioral differences across multiple behaviors. <i>Cul3</i> conditional homozygotes show repetitive jumping, reduced marble burying, increased locomotion, impaired motor coordination, and increased hindlimb clasping. We were successfully able to replicate most of these findings in an independent cohort. Our future studies are aimed at gaining mechanistic insights into <i>Cul3</i> function in the adult brain.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 5","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317486","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":"Genome-Wide Association Study of Cognitive Function in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study","authors":"Genki Shinoda,&nbsp;Taku Obara,&nbsp;Ippei Takahashi,&nbsp;Hisashi Ohseto,&nbsp;Chikana Kawaguchi,&nbsp;Akira Narita,&nbsp;Aoi Noda,&nbsp;Keiko Murakami,&nbsp;Masatsugu Orui,&nbsp;Mami Ishikuro,&nbsp;Makiko Taira,&nbsp;Hiroshi Sakamoto,&nbsp;Naoki Nakaya,&nbsp;Atsushi Hozawa,&nbsp;Nobuo Fuse,&nbsp;Gen Tamiya,&nbsp;Shunji Mugikura,&nbsp;Kyoko Suzuki,&nbsp;Shinichi Kuriyama","doi":"10.1111/gbb.70038","DOIUrl":"10.1111/gbb.70038","url":null,"abstract":"<p>Heritability of cognitive function is estimated to be 50%–80%. Genome-wide association studies (GWASs) have identified multiple cognitive function-associated loci, primarily in the European population. However, those in Asian populations, particularly in individuals of Japanese ancestry, remain limited. Hence, this GWAS aimed to identify cognitive function-associated genetic loci in elderly individuals of Japanese ancestry. Herein, 2571 elderly participants from the Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study were included. Their cognitive function was assessed using the Japanese version of the Mini-Mental State Examination (MMSE), and both binary and continuous MMSE scores were analysed. Genotyping was performed using the Affymetrix Axiom Japonica Array v2, and imputation was conducted with 3.5KJPNv2 and 1KGP3. Statistical analyses were performed using FastGWA-GLMM and FastGWA for binary and continuous MMSE scores, respectively. Although no genome-wide significant loci were identified using binary MMSE values, the following two were detected using continuous MMSE values: rs77877360 (20p12.1) near <i>BANF2</i> and <i>SNX5</i> and rs9460729 (6p22.3) near <i>PRL</i> and <i>HDGFL1</i>. Additionally, functional annotation suggested the involvement of these loci in pathways related to cognitive function, including chromatin structure regulation, neuroinflammation, and iron metabolism. Notably, <i>SNX5</i>, identified through chromatin-interaction mapping, has been implicated in neurodegenerative processes, particularly in Parkinson's disease. The findings of this study provide preliminary genome-wide evidence suggesting a genetic predisposition to impaired cognitive function in elderly Japanese individuals.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 5","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314018","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}