Genes Brain and Behavior最新文献

{"title":"Atp1a2 and Kcnj9 Are Candidate Genes Underlying Sensitivity to Oxycodone-Induced Locomotor Activation and Withdrawal-Induced Anxiety-Like Behaviors in C57BL/6 Substrains","authors":"Lisa R. Goldberg,&nbsp;Britahny M. Baskin,&nbsp;Jacob A. Beierle,&nbsp;Yahia Adla,&nbsp;Julia C. Kelliher,&nbsp;Emily J. Yao,&nbsp;Stacey L. Kirkpatrick,&nbsp;Eric R. Reed,&nbsp;David F. Jenkins,&nbsp;Jiayi Cox,&nbsp;Alexander M. Luong,&nbsp;Kimberly P. Luttik,&nbsp;Julia A. Scotellaro,&nbsp;Timothy A. Drescher,&nbsp;Sydney B. Crotts,&nbsp;Neema Yazdani,&nbsp;Martin T. Ferris,&nbsp;W. Evan Johnson,&nbsp;Megan K. Mulligan,&nbsp;Camron D. Bryant","doi":"10.1111/gbb.70009","DOIUrl":"10.1111/gbb.70009","url":null,"abstract":"<p>Opioid use disorder is heritable, yet its genetic etiology is largely unknown. C57BL/6J and C57BL/6NJ mouse substrains exhibit phenotypic diversity in the context of limited genetic diversity which together can facilitate genetic discovery. Here, we found C57BL/6NJ mice were less sensitive to oxycodone (OXY)-induced locomotor activation versus C57BL/6J mice in a conditioned place preference paradigm. Narrow-sense heritability of OXY-induced locomotor activity traits ranged from 0.22 to 0.31, implicating suitability for genetic analysis. Quantitative trait locus (QTL) mapping in an F2 cross identified a chromosome 1 QTL explaining 7%–12% of the variance in OXY locomotion and anxiety-like withdrawal in the elevated plus maze. A second QTL for EPM withdrawal behavior on chromosome 5 near <i>Gabra2</i> (alpha-2 subunit of GABA-A receptor) explained 9% of the variance. To narrow the chromosome 1 locus, we generated recombinant lines spanning 163–181 Mb, captured the QTL for OXY locomotor traits and withdrawal, and fine-mapped a 2.45-Mb region (170.16–172.61 Mb). Transcriptome analysis identified five, localized striatal cis-eQTL transcripts and two were confirmed at the protein level (KCNJ9, ATP1A2). <i>Kcnj9</i> codes for a potassium channel (GIRK3) that is a major effector of mu opioid receptor signaling. <i>Atp1a2</i> codes for a subunit of a Na+/K+ ATPase enzyme that regulates neuronal excitability and shows functional adaptations following chronic opioid administration. To summarize, we identified two candidate genes underlying the physiological and behavioral properties of opioids, with direct preclinical relevance to investigators employing these widely used substrains and clinical relevance to human genetic studies of opioid use disorder.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973120","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":"Understanding the Emergence of Schizophrenia in the Light of Human Evolution: New Perspectives in Genetics","authors":"Veronica Sandroni,&nbsp;Boris Chaumette","doi":"10.1111/gbb.70013","DOIUrl":"10.1111/gbb.70013","url":null,"abstract":"<p>Schizophrenia is a frequent and disabling disease. The persistence of the disorder despite its harmful consequences represents an evolutionary paradox. Based on recent discoveries in genetics, scientists have formulated the “price-to-pay” hypothesis: schizophrenia would be intimately related to human evolution, particularly to brain development and human-specific higher cognitive functions. The objective of the present work is to question scientific literature about the relationship between schizophrenia and human evolution from a genetic point of view. In the last two decades, research investigated the association between schizophrenia and a few genetic evolutionary markers: Human accelerated regions, segmental duplications, and highly repetitive DNA such as the Olduvai domain. Other studies focused on the action of natural selection on schizophrenia-associated genetic variants, also thanks to the complete sequencing of archaic hominins' genomes (Neanderthal, Denisova). Results suggested that a connection between human evolution and schizophrenia may exist; nonetheless, much research is still needed, and it is possible that a definitive answer to the evolutionary paradox of schizophrenia will never be found.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973122","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":"Fecal Microbiota Transplantation (FMT) From a Human at Low Risk for Alzheimer's Disease Improves Short-Term Recognition Memory and Increases Neuroinflammation in a 3xTg AD Mouse Model","authors":"Claire Chevalier,&nbsp;Benjamin B. Tournier,&nbsp;Moira Marizzoni,&nbsp;Rahel Park,&nbsp;Arthur Paquis,&nbsp;Kelly Ceyzériat,&nbsp;Aurélien M. Badina,&nbsp;Aurelien Lathuiliere,&nbsp;Samantha Saleri,&nbsp;Floriana De Cillis,&nbsp;Annamaria Cattaneo,&nbsp;Philippe Millet,&nbsp;Giovanni B. Frisoni","doi":"10.1111/gbb.70012","DOIUrl":"10.1111/gbb.70012","url":null,"abstract":"<p>Human microbiota-associated murine models, using fecal microbiota transplantation (FMT) from human donors, help explore the microbiome's role in diseases like Alzheimer's disease (AD). This study examines how gut bacteria from donors with protective factors against AD influence behavior and brain pathology in an AD mouse model. Female 3xTgAD mice received weekly FMT for 2 months from (i) an 80-year-old AD patient (AD-FMT), (ii) a cognitively healthy 73-year-old with the protective APOEe2 allele (APOEe2-FMT), (iii) a 22-year-old healthy donor (Young-FMT), and (iv) untreated mice (Mice-FMT). Behavioral assessments included novel object recognition (NOR), Y-maze, open-field, and elevated plus maze tests; brain pathology (amyloid and tau), neuroinflammation (in situ autoradiography of the 18 kDa translocator protein in the hippocampus); and gut microbiota were analyzed. APOEe2-FMT improved short-term memory in the NOR test compared to AD-FMT, without significant changes in other behavioral tests. This was associated with increased neuroinflammation in the hippocampus, but no effect was detected on brain amyloidosis and tauopathy. Specific genera, such as <i>Parabacteroides</i> and <i>Prevotellaceae_UGC001</i>, were enriched in the APOEe2-FMT group and associated with neuroinflammation, while genera like <i>Desulfovibrio</i> were reduced and linked to decreased neuroinflammation. Gut microbiota from a donor with a protective factor against AD improved short-term memory and induced neuroinflammation in regions strategic to AD. The association of several genera with neuroinflammation in the APOEe2-FMT group suggests a collegial effect of the transplanted microbiome rather than a single-microbe driver effect. These data support an association between gut bacteria, glial cell activation, and cognitive function in AD.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973121","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":"Role of Odor Novelty on Olfactory Issues in Autism Spectrum Disorder","authors":"Zoe A. Scheier,&nbsp;Kassandra L. Sturm,&nbsp;John A. Colavecchio,&nbsp;Apekchha Pradhan,&nbsp;Gonzalo H. Otazu","doi":"10.1111/gbb.70008","DOIUrl":"10.1111/gbb.70008","url":null,"abstract":"<p>Sensory processing abnormalities are a hallmark of autism spectrum disorder (ASD) and are included in its diagnostic criteria. Among these challenges, food neophobia has garnered attention due to its prevalence and potential impact on nutritional intake and health outcomes. This review describes the correlation between novel odor perception and feeding difficulties within the context of ASD. Moreover, this review underscores the role of odor processing in shaping feeding behaviors within the ASD population. It examines the psychophysics of odor perception in individuals with ASD and evaluates the behavioral and neurophysiological assessments conducted using novel odor stimuli in mouse models relevant to autism and wild-type mice. Additionally, we explore the mechanism on how odor novelty affects neuronal circuitry, shedding light on potential underlying mechanisms for the effect of odor novelty on ASD.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900146","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 Sleep, Neurodevelopmental and Neuropsychiatric Conditions: A Genome-Wide and Pathway-Based Polygenic Score Analysis","authors":"Laura Fahey,&nbsp;Lorna M. Lopez","doi":"10.1111/gbb.70011","DOIUrl":"10.1111/gbb.70011","url":null,"abstract":"<p>Genetic correlations have been reported between chronotype and both autism (AUT) and schizophrenia (SCZ), as well as between insomnia and attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BP), schizophrenia (SCZ) and major depression (MDD). Our study aimed to investigate these shared genetic variations using genome-wide and pathway-based polygenic score analyses. We computed polygenic scores using summary statistics from genome-wide association studies (GWAS) of ADHD (<i>N</i> = 225,534), AUT (<i>N</i> = 46,350), BP (<i>N</i> = 353,899), MDD (<i>N</i> = 500,199) and SCZ (<i>N</i> = 160,779). We tested their performance in predicting chronotype (<i>N</i> = 409,630) and insomnia (<i>N</i> = 239,918) status of UK Biobank participants. For pathway-based polygenic scores, we restricted genetic variation to SNPs that mapped to genes within 1377 Reactome pathways. Genome-wide polygenic scores for AUT, BP, MDD and SCZ were associated with an evening chronotype (<i>p</i> &lt; 2.2 × 10⁻¹⁶, <i>p</i> = 4.8 × 10⁻³, <i>p</i> = 8.07 × 10⁻⁴ and <i>p</i> &lt; 2.2 × 10⁻¹⁶, respectively). Polygenic scores for ADHD, AUT, BP, MDD SCZ were associated with insomnia (<i>p</i> &lt; 2.2 × 10⁻¹⁶, <i>p</i> = 2.93 × 10⁻³, <i>p</i> = 2.9 × 10⁻⁷, <i>p</i> &lt; 2.2 × 10⁻¹⁶ and <i>p</i> = 8.86 × 10⁻³, respectively). While pathway-based polygenic score analysis identified the KEAP1-NRF2 (<i>p</i> = 1.29 × 10⁻⁸) and mRNA Splicing-Minor Pathways (<i>p</i> = 1.52 × 10⁻⁸) as enriched for genetic variation overlapping between chronotype and BP, the majority of tested pathways yielded null findings, suggesting that specific shared genetic mechanisms between sleep-related phenotypes and neurodevelopmental/psychiatric conditions (NDPC) may be limited to a subset of pathways. Colocalisation analysis identified BP-associated SNPs in <i>CUL3</i> and <i>SF3B1</i> as being linked to changes in their expression. Our results strengthen evidence for shared genetic variation between NDPC and sleep-related phenotypes. We identify the KEAP1-NRF2 and mRNA Splicing-Minor Pathways as potentially mediating the disrupted circadian rhythm phenotype of BP.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900147","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 brain atlas of a subsocial bee reflects that of eusocial Hymenoptera","authors":"Benjamin C. Pyenson,&nbsp;Jesse L. Huisken,&nbsp;Nandini Gupta,&nbsp;Sandra M. Rehan","doi":"10.1111/gbb.70007","DOIUrl":"10.1111/gbb.70007","url":null,"abstract":"<p>The evolutionary transition from solitary life to group-living in a society with cooperative brood care, reproductive division of labor and morphological castes is associated with increased cognitive demands for task-specialization. Associated with these demands, the brains of eusocial Hymenoptera divide transcriptomic signatures associated with foraging and reproduction to different populations of cells and also show diverse astrocyte and Kenyon cell types compared with solitary non-hymenopteran insects. The neural architecture of subsocial bees, which represent evolutionary antecedent states to eusocial Hymenoptera, could then show how widely this eusocial brain is conserved across aculeate Hymenoptera. Using single-nucleus transcriptomics, we have created an atlas of neuron and glial cell types from the brain of a subsocial insect, the small carpenter bee (<i>Ceratina calcarata</i>). The proportion of <i>C. calcarata</i> neurons related to the metabolism of classes of neurotransmitters is similar to that of other insects, whereas astrocyte and Kenyon cell types show highly similar gene expression patterns to those of eusocial Hymenoptera. In the winter, the transcriptomic signature across the brain reflected diapause. When the bee was active in the summer, however, genes upregulated in neurons reflected foraging, while the gene expression signature of glia associated with reproductive functions. Like eusocial Hymenoptera, we conclude that neural components for foraging and reproduction in <i>C. calcarata</i> are compartmentalized to different parts of its brain. Cellular examination of the brains of other solitary and subsocial insects can show the extent of neurobiological conservation across levels of social complexity.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607364","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":"Stress enhances aggression in male rats with genetic stress hyper-reactivity","authors":"Aspen M. Harter,&nbsp;Chris Kim,&nbsp;Anna Yamazaki,&nbsp;Luca Lee,&nbsp;Michelle T. Ji,&nbsp;Mariya Nemesh,&nbsp;Eva E. Redei","doi":"10.1111/gbb.70005","DOIUrl":"https://doi.org/10.1111/gbb.70005","url":null,"abstract":"<p>The current study investigated stress-induced aggressive behavior in the resident-intruder test in males of the genetically stress hyper-reactive Wistar Kyoto More Immobile (WMI), and the nearly isogenic, control Wistar Kyoto Less Immobile (WLI) strains. Tests were carried out against same-age intruders during adolescence, and same-age and juvenile intruders in adulthood. In adolescence and adulthood, prior acute restraint stress decreased social interactions and decreased aggressive behaviors of adolescents and adult WLIs. However, prior stress precipitated aggression in the adult WMI males toward both same-age, and juvenile intruders compared with control WMIs and WLIs. Trunk blood levels of testosterone and androstenedione increased in stressed WLIs, but not in WMIs, suggesting no direct role of androgens in the increased aggression of WMIs. Expressions of aggression-relevant genes showed patterns commensurate with being causative in aggressive behavior. The methyl-CpG binding protein 2 was lower in the frontal cortex of control WMIs, and in the amygdala of stressed WMIs compared with their respective WLIs. Frontal cortex expression of vasopressin receptor 1a and serotonin transporter increased, solely in WMI males after stress. As behaviors were the same toward same-age and non-threatening juvenile intruders, the stress-induced increase in confrontational behavior of the adult WMI male was not because of enhanced fear or anxiety. These results suggest that genetic stress hyper-reactivity is a risk factor for stress-induced increases in aggression in males. Additionally, as known aggression-related genes showed expression patterns paralleling aggressive behavior, this model system could identify novel molecular pathways leading to stress-enhanced aggression.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451154","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 role of cerebellar FOXP1 in the development of motor and communicative behaviors in mice","authors":"R. Chasse,&nbsp;R. McLeod,&nbsp;A. Surian,&nbsp;R. H. Fitch,&nbsp;J. Li","doi":"10.1111/gbb.70001","DOIUrl":"https://doi.org/10.1111/gbb.70001","url":null,"abstract":"<p>The gene <i>FOXP2</i> is well established for a role in human speech and language; far less is known about <i>FOXP1</i>. However, this related gene has also been implicated in human language development as well as disorders associated with features of autism spectrum disorder (ASD). FOXP1 protein expression has also recently been identified in the cerebellum—a neural structure previously shown to express FOXP2 protein. The current study sought to elucidate the behavioral implications of a conditional knock-out of <i>Foxp1</i> using an <i>En1-Cre</i> driver, which is active in the entirety of the cerebellum and a subset of neurons in the midbrain and spinal cord, in mice using a test battery including motor tasks associated with cerebellar dysfunction, as well as communicative and autistic-relevant behaviors. Male and female mice with a conditional knock-out (cKO, <i>n</i> = 31) and wildtype littermate controls (WT, <i>n</i> = 34) were assessed for gross and orofacial motor control, motor-coordination learning, locomotion, social behavior, anxiety, auditory processing and expressive vocalizations. Overall results suggest <i>Foxp1</i> plays a specific role in the development of communicative systems, and phenotypic expression of disruptions may interact with sex. Robust motor deficits associated with Foxp1 protein loss may particularly affect vocalizations based on significant orofacial motor deficits in cKO subjects could also contribute to vocalization anomalies. In summary, the current study provides key insights into the role of <i>Foxp1</i> in cerebellar function and associated behaviors in mice, with implications for an improved understanding of communicative and motor-based neurodevelopmental disabilities in humans.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443372","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":"Concentration- and time-dependent behavioural effects of ethanol on Lumbriculus variegatus","authors":"Aidan Seeley,&nbsp;Romessa Mahmood,&nbsp;Caitlin Bellamy,&nbsp;Elis G. Roome,&nbsp;Benjamin S. Williams,&nbsp;Nia A. Davies,&nbsp;Melisa J. Wallace","doi":"10.1111/gbb.70006","DOIUrl":"https://doi.org/10.1111/gbb.70006","url":null,"abstract":"<p>Ethanol is one of the most widely used drugs in the world. Ethanol induces profound physiological and behavioural responses in invertebrate model organisms, such as <i>Caenorhabditis elegans</i> and <i>Drosophila melanogaster</i>. <i>Lumbriculus variegatus</i> (Annelida, Oligochaete) is an aquatic worm which shows behavioural responses to common drugs and thus is potentially useful in pharmacological research. The effects of ethanol are unknown in this organism. In this study, we examine the effects of acute exposure to ethanol (0–500 mM) on the stereotypical movements and locomotor activity of <i>L. variegatus</i> and examine the concentration- (0–500 mM) and time-dependent (0–210 min) effects of ethanol in <i>L. variegatus</i>. We show that ≥250 mM ethanol reversibly reduced the ability of tactile stimulation to elicit stereotypical movements, namely body reversal and helical swimming and locomotor activity (<i>p</i> &lt; 0.05, <i>N</i> = 8). We also found that 2 min of exposure to ≥250 mM ethanol rapidly induces steady-state hypokinesis (<i>p</i> &lt; 0.05, <i>N</i> = 11) and confirm ethanol absorption into <i>L. variegatus</i> tissues. Additionally, we also observed acute ethanol tolerance after 150 min of exposure to 500 mM ethanol (<i>p</i> &lt; 0.05, <i>N</i> = 24). This study is the first to report the behavioural effects of ethanol in <i>L. variegatus</i>. Our results show that this is a model organism for use in ethanol studies, providing further evidence for its utility in pharmacological research.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443373","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":"A GWAS for grip strength in cohorts of children—Advantages of analysing young participants for this trait","authors":"Filippo Abbondanza,&nbsp;Carol A. Wang,&nbsp;Judith Schmitz,&nbsp;Krzysztof Marianski,&nbsp;Craig E. Pennell,&nbsp;Andrew J. O. Whitehouse,&nbsp;Silvia Paracchini","doi":"10.1111/gbb.70003","DOIUrl":"10.1111/gbb.70003","url":null,"abstract":"<p>Grip strength (GS) is a proxy measure for muscular strength and a predictor for bone fracture risk among other diseases. Previous genome-wide association studies (GWASs) have been conducted in large cohorts of adults focusing on scores collected for the dominant hand, therefore increasing the likelihood of confounding effects by environmental factors. Here, we perform the first GWAS meta-analyses on maximal GS with the dominant (GSD) and non-dominant (GSND) hand in two cohorts of children (ALSPAC, <i>N</i> = 5450; age range = 10.65–13.61; Raine Study, <i>N</i> = 1162, age range: 9.42–12.38 years). We identified a novel significant association for GSND (rs9546244, <i>LINC02465</i>, <i>p</i> = 3.43e−08<i>)</i> and replicated associations previously reported in adults including with a <i>HOXB3</i> gene marker that shows an expression quantitative trait locus (eQTL) effect. Despite a much smaller sample (~3%) compared with the UK Biobank we replicated correlation analyses previously reported in this much larger adult cohort, such as a negative correlation with coronary artery disease. Although the results from the polygenic risk score (PRS) analyses did not survive multiple testing correction, we observed nominally significant associations between GS and risk of overall fracture, as previously reported, as well ADHD which will require further investigations. Finally, we observed a higher SNP-heritability (24%–41%) compared with previous studies (4%–24%) in adults. Overall, our results suggest that cohorts of children might be better suited for genetic studies of grip strength, possibly due to the shorter exposure to confounding environmental factors compared with adults.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394899","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}