Genes Brain and Behavior最新文献

{"title":"A mild impairment in reversal learning in a bowl-digging substrate deterministic task but not other cognitive tests in the Dlg2+/− rat model of genetic risk for psychiatric disorder","authors":"Simonas Griesius,&nbsp;Sophie Waldron,&nbsp;Katie A. Kamenish,&nbsp;Nick Cherbanich,&nbsp;Lawrence S. Wilkinson,&nbsp;Kerrie L. Thomas,&nbsp;Jeremy Hall,&nbsp;Jack R. Mellor,&nbsp;Dominic M. Dwyer,&nbsp;Emma S. J. Robinson","doi":"10.1111/gbb.12865","DOIUrl":"10.1111/gbb.12865","url":null,"abstract":"<p>Variations in the Dlg2 gene have been linked to increased risk for psychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability, bipolar disorder, attention deficit hyperactivity disorder, and pubertal disorders. Recent studies have reported disrupted brain circuit function and behaviour in models of Dlg2 knockout and haploinsufficiency. Specifically, deficits in hippocampal synaptic plasticity were found in heterozygous Dlg2+/− rats suggesting impacts on hippocampal dependent learning and cognitive flexibility. Here, we tested these predicted effects with a behavioural characterisation of the heterozygous Dlg2+/− rat model. Dlg2+/− rats exhibited a specific, mild impairment in reversal learning in a substrate deterministic bowl-digging reversal learning task. The performance of Dlg2+/− rats in other bowl digging task, visual discrimination and reversal, novel object preference, novel location preference, spontaneous alternation, modified progressive ratio, and novelty-suppressed feeding test were not impaired. These findings suggest that despite altered brain circuit function, behaviour across different domains is relatively intact in Dlg2+/− rats, with the deficits being specific to only one test of cognitive flexibility. The specific behavioural phenotype seen in this Dlg2+/− model may capture features of the clinical presentation associated with variation in the Dlg2 gene.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12865","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286215","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 collaborative study on the genetics of alcoholism: Brain function","authors":"Jacquelyn L. Meyers,&nbsp;Sarah J. Brislin,&nbsp;Chella Kamarajan,&nbsp;Martin H. Plawecki,&nbsp;David Chorlian,&nbsp;Andrey Anohkin,&nbsp;Samuel Kuperman,&nbsp;Alison Merikangas,&nbsp;Gayathri Pandey,&nbsp;Sivan Kinreich,&nbsp;Ashwini Pandey,&nbsp;Howard J. Edenberg,&nbsp;Kathleen K. Bucholz,&nbsp;COGA Collaborators,&nbsp;Laura Almasy,&nbsp;Bernice Porjesz","doi":"10.1111/gbb.12862","DOIUrl":"10.1111/gbb.12862","url":null,"abstract":"<p>Alcohol use disorder (AUD) and related health conditions result from a complex interaction of genetic, neural and environmental factors, with differential impacts across the lifespan. From its inception, the Collaborative Study on the Genetics of Alcoholism (COGA) has focused on the importance of brain function as it relates to the risk and consequences of alcohol use and AUD, through the examination of noninvasively recorded brain electrical activity and neuropsychological tests. COGA's sophisticated neurophysiological and neuropsychological measures, together with rich longitudinal, multi-modal family data, have allowed us to disentangle brain-related risk and resilience factors from the consequences of prolonged and heavy alcohol use in the context of genomic and social-environmental influences over the lifespan. COGA has led the field in identifying genetic variation associated with brain functioning, which has advanced the understanding of how genomic risk affects AUD and related disorders. To date, the COGA study has amassed brain function data on over 9871 participants, 7837 with data at more than one time point, and with notable diversity in terms of age (from 7 to 97), gender (52% female), and self-reported race and ethnicity (28% Black, 9% Hispanic). These data are available to the research community through several mechanisms, including directly through the NIAAA, through dbGAP, and in collaboration with COGA investigators. In this review, we provide an overview of COGA's data collection methods and specific brain function measures assessed, and showcase the utility, significance, and contributions these data have made to our understanding of AUD and related disorders, highlighting COGA research findings.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12862","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10105392","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 collaborative study on the genetics of alcoholism: Sample and clinical data","authors":"Danielle M. Dick,&nbsp;Emily Balcke,&nbsp;Vivia McCutcheon,&nbsp;Meredith Francis,&nbsp;Sally Kuo,&nbsp;Jessica Salvatore,&nbsp;Jacquelyn Meyers,&nbsp;Laura J. Bierut,&nbsp;Marc Schuckit,&nbsp;Victor Hesselbrock,&nbsp;Howard J. Edenberg,&nbsp;Bernice Porjesz,&nbsp;COGA Collaborators,&nbsp;Samuel Kuperman,&nbsp;John Kramer,&nbsp;Kathleen Bucholz","doi":"10.1111/gbb.12860","DOIUrl":"10.1111/gbb.12860","url":null,"abstract":"<p>The collaborative study on the genetics of alcoholism (COGA) is a multi-site, multidisciplinary project with the goal of identifying how genes are involved in alcohol use disorder and related outcomes, and characterizing how genetic risk unfolds across development and in conjunction with the environment and brain function. COGA is a multi-generational family-based study in which probands were recruited through alcohol treatment centers, along with a set of community comparison families. Nearly 18,000 individuals from &gt;2200 families have been assessed over a period of over 30 years with a rich phenotypic battery that includes semi-structured psychiatric interviews and questionnaire measures, along with DNA collection and electrophysiological data on a large subset. Participants range in age from 7 to 97, with many having longitudinal assessments, providing a valuable opportunity to study alcohol use and problems across the lifespan. Here we provide an overview of data collection methods for the COGA sample, and details about sample characteristics and comorbidity. We also review key research findings that have emerged from analyses of the COGA data. COGA data are available broadly to researchers, and we hope this overview will encourage further collaboration and use of these data to advance the field.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/38/GBB-22-e12860.PMC10550787.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997850","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":"Impaired erythropoietin-producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats","authors":"Yiqian Shao,&nbsp;Yaqi Cai,&nbsp;Tengfei Chen,&nbsp;Keke Hao,&nbsp;Binbin Luo,&nbsp;Xiujuan Wang,&nbsp;Weiyun Guo,&nbsp;Xi Su,&nbsp;Luxian Lv,&nbsp;Yongfeng Yang,&nbsp;Wenqiang Li","doi":"10.1111/gbb.12863","DOIUrl":"10.1111/gbb.12863","url":null,"abstract":"<p>An environmental risk factor for schizophrenia (SZ) is maternal infection, which exerts longstanding effects on the neurodevelopment of offspring. Accumulating evidence suggests that synaptic disturbances may contribute to the pathology of the disease, but the underlying molecular mechanisms remain poorly understood. Erythropoietin-producing hepatocellular B (EphB) receptor signaling plays an important role in synaptic plasticity by regulating the formation and maturation of dendritic spines and regulating excitatory neurotransmission. We examined whether EphB receptors and downstream associated proteins are susceptible to environmental risk factors implicated in the etiology of synaptic disturbances in SZ. Using an established rodent model, which closely imitates the characteristics of SZ, we observed the behavioral performance and synaptic structure of male offspring in adolescence and early adulthood. We then analyzed the expression of EphB receptors and associated proteins in the prefrontal cortex and hippocampus. Maternal immune activation offspring showed significantly progressive cognitive impairment and pre-pulse inhibition deficits together with an increase in the expression of EphB2 receptors and NMDA receptor subunits. We also found changes in EphB receptor downstream signaling, in particular, a decrease in phospho-cofilin levels which may explain the reduced dendritic spine density. Besides, we found that the AMPA glutamate, another glutamate ionic receptor associated with cofilin, decreased significantly in maternal immune activation offspring. Thus, alterations in EphB signaling induced by immune activation during pregnancy may underlie disruptions in synaptic plasticity and function in the prefrontal cortex and hippocampus associated with behavioral and cognitive impairment. These findings may provide insight into the mechanisms underlying SZ.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12863","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10362692","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":"Developmental coordination disorder: What can we learn from RI mice using motor learning tasks and QTL analysis","authors":"Kamaldeep Gill,&nbsp;Jeffy Rajan Soundara Rajan,&nbsp;Eric Chow,&nbsp;David G. Ashbrook,&nbsp;Robert W. Williams,&nbsp;Jill G. Zwicker,&nbsp;Daniel Goldowitz","doi":"10.1111/gbb.12859","DOIUrl":"10.1111/gbb.12859","url":null,"abstract":"<p>Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder of unknown etiology that affects one in 20 children. There is an indication that DCD has an underlying genetic component due to its high heritability. Therefore, we explored the use of a recombinant inbred family of mice known as the BXD panel to understand the genetic basis of complex traits (i.e., motor learning) through identification of quantitative trait loci (QTLs). The overall aim of this study was to utilize the QTL approach to evaluate the genome-to-phenome correlation in BXD strains of mice in order to better understand the human presentation of DCD. Results of this current study confirm differences in motor learning in selected BXD strains and strains with altered cerebellar volume. Five strains – BXD15, BXD27, BXD28, BXD75, and BXD86 – exhibited the most DCD-like phenotype when compared with other BXD strains of interest. Results indicate that BXD15 and BXD75 struggled primarily with gross motor skills, BXD28 primarily had difficulties with fine motor skills, and BXD27 and BXD86 strains struggled with both fine and gross motor skills. The functional roles of genes within significant QTLs were assessed in relation to DCD-like behavior. Only <i>Rab3a</i> (Ras-related protein Rab-3A) emerged as a high likelihood candidate gene for the horizontal ladder rung task. This gene is associated with brain and skeletal muscle development, but lacked nonsynonymous polymorphisms. This study along with Gill et al. (same issue) is the first studies to specifically examine the genetic linkage of DCD using BXD strains of mice.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12859","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960199","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":"5. Collaborative Study on the Genetics of Alcoholism: Functional genomics","authors":"Isabel Gameiro-Ros,&nbsp;Dina Popova,&nbsp;Iya Prytkova,&nbsp;Zhiping P. Pang,&nbsp;Yunlong Liu,&nbsp;Danielle Dick,&nbsp;Kathleen K. Bucholz,&nbsp;Arpana Agrawal,&nbsp;Bernice Porjesz,&nbsp;Alison M. Goate,&nbsp;Xiaoling Xuei,&nbsp;Chella Kamarajan,&nbsp;COGA Collaborators,&nbsp;Jay A. Tischfield,&nbsp;Howard J. Edenberg,&nbsp;Paul A. Slesinger,&nbsp;Ronald P. Hart","doi":"10.1111/gbb.12855","DOIUrl":"10.1111/gbb.12855","url":null,"abstract":"<p>Alcohol Use Disorder is a complex genetic disorder, involving genetic, neural, and environmental factors, and their interactions. The Collaborative Study on the Genetics of Alcoholism (COGA) has been investigating these factors and identified putative alcohol use disorder risk genes through genome-wide association studies. In this review, we describe advances made by COGA in elucidating the functional changes induced by alcohol use disorder risk genes using multimodal approaches with human cell lines and brain tissue. These studies involve investigating gene regulation in lymphoblastoid cells from COGA participants and in post-mortem brain tissues. High throughput reporter assays are being used to identify single nucleotide polymorphisms in which alternate alleles differ in driving gene expression. Specific single nucleotide polymorphisms (both coding or noncoding) have been modeled using induced pluripotent stem cells derived from COGA participants to evaluate the effects of genetic variants on transcriptomics, neuronal excitability, synaptic physiology, and the response to ethanol in human neurons from individuals with and without alcohol use disorder. We provide a perspective on future studies, such as using polygenic risk scores and populations of induced pluripotent stem cell-derived neurons to identify signaling pathways related with responses to alcohol. Starting with genes or loci associated with alcohol use disorder, COGA has demonstrated that integration of multimodal data within COGA participants and functional studies can reveal mechanisms linking genomic variants with alcohol use disorder, and potential targets for future treatments.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/5a/GBB-22-e12855.PMC10550792.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042569","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":"Partner-seeking and limbic dopamine system are enhanced following social loss in male prairie voles (Microtus ochrogaster)","authors":"Erika M. Vitale,&nbsp;Adrianna Kirckof,&nbsp;Adam S. Smith","doi":"10.1111/gbb.12861","DOIUrl":"10.1111/gbb.12861","url":null,"abstract":"<p>Death of a loved one is recognized as one of life's greatest stresses, and 10%–20% of bereaved individuals will experience a complicated or prolonged grieving period that is characterized by intense yearning for the deceased. The monogamous prairie vole (<i>Microtus ochrogaster</i>) is a rodent species that forms pair bonds between breeding partners and has been used to study the neurobiology of social behaviors and isolation. Male prairie voles do not display distress after isolation from a familiar, same-sex conspecific; however, separation from a bonded female partner increases emotional, stress-related, and proximity-seeking behaviors. Here, we tested the investigatory response of male voles to partner odor during a period of social loss. We found that males who lost their partner spent significantly more time investigating partner odor but not non-partner social odor or food odor. Bachelor males and males in intact pairings did not respond uniquely to any odor. Furthermore, we examined dopamine (DA) receptor mRNA expression in the anterior insula cortex (aIC), nucleus accumbens (NAc), and anterior cingulate (ACC), regions with higher activation in grieving humans. While we found some effects of relationship type on DRD1 and DRD2 expression in some of these regions, loss of a high-quality opposite-sex relationship had a significant effect on DA receptor expression, with pair-bonded/loss males having higher expression in the aIC and ACC compared with pair-bonded/intact and nonbonded/loss males. Together, these data suggest that both relationship type and relationship quality affect reunion-seeking behavior and motivational neurocircuits following social loss of a bonded partner.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12861","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10274164","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":"Maternal upbringing and selective breeding for voluntary exercise behavior modify patterns of DNA methylation and expression of genes in the mouse brain","authors":"Sarah E. Latchney,&nbsp;Marcell D. Cadney,&nbsp;Anthony Hopkins,&nbsp;Theodore Garland Jr","doi":"10.1111/gbb.12858","DOIUrl":"10.1111/gbb.12858","url":null,"abstract":"<p>Selective breeding has been utilized to study the genetic basis of exercise behavior, but research suggests that epigenetic mechanisms, such as DNA methylation, also contribute to this behavior. In a previous study, we demonstrated that the brains of mice from a genetically selected high runner (HR) line have sex-specific changes in DNA methylation patterns in genes known to be genomically imprinted compared to those from a non-selected control (C) line. Through cross-fostering, we also found that maternal upbringing can modify the DNA methylation patterns of additional genes. Here, we identify an additional set of genes in which DNA methylation patterns and gene expression may be altered by selection for increased wheel-running activity and maternal upbringing. We performed bisulfite sequencing and gene expression assays of 14 genes in the brain and found alterations in DNA methylation and gene expression for <i>Bdnf</i>, <i>Pde4d</i> and <i>Grin2b</i>. Decreases in <i>Bdnf</i> methylation correlated with significant increases in <i>Bdnf</i> gene expression in the hippocampus of HR compared to C mice. Cross-fostering also influenced the DNA methylation patterns for <i>Pde4d</i> in the cortex and <i>Grin2b</i> in the hippocampus, with associated changes in gene expression. We also found that the DNA methylation patterns for <i>Atrx</i> and <i>Oxtr</i> in the cortex and <i>Atrx</i> and <i>Bdnf</i> in the hippocampus were further modified by sex. Together with our previous study, these results suggest that DNA methylation and the resulting change in gene expression may interact with early-life influences to shape adult exercise behavior.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12858","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9897853","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":"Patterns of ethanol intake in male rats with partial dopamine transporter deficiency","authors":"L. B. Kuiper,&nbsp;J. B. Roberts,&nbsp;P. M. Estave,&nbsp;D. Leo,&nbsp;R. R. Gainetdinov,&nbsp;S. R. Jones","doi":"10.1111/gbb.12847","DOIUrl":"10.1111/gbb.12847","url":null,"abstract":"<p>Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/−) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/− rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/− rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/− males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9824706","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 impact of early adversity and education on genetic and brain morphological predictors of cognitive ability","authors":"Emma Corley,&nbsp;Laura Fahey,&nbsp;Joan Fitzgerald,&nbsp;Laurena Holleran,&nbsp;Esther Walton,&nbsp;Derek W. Morris,&nbsp;Gary Donohoe","doi":"10.1111/gbb.12850","DOIUrl":"10.1111/gbb.12850","url":null,"abstract":"<p>Cognitive ability is a strong predictor of occupational achievement, quality of life and physical health. While variation in cognition is strongly heritable and has been robustly associated with early environment and brain morphology, little is known about how these factors combine and interact to explain this variation in cognition. To address this, we modelled the relationship between common genetic variation, grey matter volume, early life adversity and education and cognitive ability in a UK Biobank sample of <i>N</i> = 5237 individuals using structural equation modelling. We tested the hypotheses that total grey matter volume would mediate the association between genetic variation and cognitive ability, and that early life adversity and educational attainment would moderate this relationship. Common genetic variation, grey matter volume and early life adversity were each significant predictors in the model, explaining ~15% of variation in cognitive ability. Contrary to our hypothesis, grey matter volume did not mediate the relation between genetic variation and cognition performance. Neither did early life adversity or educational attainment moderate this relation, although educational attainment was observed to moderate the relationship between grey matter volume and cognitive performance. We interpret these findings in terms of the modest explanatory value of currently estimated polygenic scores accounting for variation in cognitive performance (~5%), making potential mediating and moderating variables difficult to confirm.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923818","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}