A systems biology approach to identify intelligence quotient score-related genomic regions, and pathways relevant to potential therapeutic treatments.
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ABSTRACT:
SUBMITTER: Zhao M
PROVIDER: S-EPMC3933868 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:Intelligence quotient (IQ) is the most widely used phenotype to characterize human cognitive abilities. Recent advances in studies on human intelligence have identified many new susceptibility genes. However, the genetic mechanisms involved in IQ score and the relationship between IQ score and the risk of mental disorders have won little attention. To address the genetic complexity of IQ score, we have developed IQdb (http://IQdb.cbi.pku.edu.cn), a publicly available database for exploring IQ-associated human genes. In total, we collected 158 experimental verified genes from literature as a core dataset in IQdb. In addition, 46 genomic regions related to IQ score have been curated from literature. Based on the core dataset and 46 confirmed linked genomic regions, more than 6932 potential IQ-related genes are expanded using data of protein-protein interactions. A systematic gene ranking approach was applied to all the collected and expanded genes to represent the relative importance of all the 7090 genes in IQdb. Our further systematic pathway analysis reveals that IQ-associated genes are significantly enriched in multiple signal events, especially related to cognitive systems. Of the 158 genes in the core dataset, 81 are involved in various psychotic and mental disorders. This comprehensive gene resource illustrates the importance of IQdb to our understanding on human intelligence, and highlights the utility of IQdb for elucidating the functions of IQ-associated genes and the cross-talk mechanisms among cognition-related pathways in some mental disorders for community. Database URL: http://IQdb.cbi.pku.edu.cn.
| S-EPMC3770929 | biostudies-literature
Project description:This research explored how intelligence interviewees mentally identify the relevant information at their disposal. We theorized that interviewees estimate the interviewer's objectives based on how they frame any attempt to solicit information. Then interviewees organize the information they possess into item designations that pragmatically correspond to the perceived interviewer-objective. The more an interviewer specifies what they want to know, the more the interviewee will mentally designate information items corresponding with that objective. To examine the theory, we conducted two identical experiments wherein participants assumed the role of an informant with one of two dispositions. They were to be cooperative or resistant when undergoing an interview. The interviewer posed specific or ambiguous questions. In Study 1 (N = 210), interviewees identified applicable information items based on their interviewer's questions. And interviewees answered their interviewer's questions in Study 2 (N = 199). We aimed to demonstrate that question type influences mental designations and disposition affects disclosures. Disposition had a stronger influence on interviewees' disclosure than when reasoning about what the interviewer wants to know. But contrary to our expectations, mental designation preferences indicated that interviewees generally assume interviewers want to know complete details, irrespective of question specificity. We suggest avenues for future research.
| S-EPMC10427824 | biostudies-literature
Project description:This study investigated the effect of Mahjong, which is a table game played by three or four players and involves intellectual activity, on the intelligence quotient (IQ) of children. The participants were children between the age of 6 and 15 years, and their IQ was assessed immediately after enrolling in children's Mahjong classes and 1 year after the enrollment using the Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV). Twenty children were included in the analysis. Their mean age at the time of the initial evaluation was 9 years and 6 months. In addition, we conducted a 1-year post-examination. The change in the IQ of this group was compared to that of a historical control group with a similar age range and test–retest interval. The mean overall full-scale IQ of the 20 children during the initial and post-1-year examinations was 106.05 and 113.75, respectively, and showed a statistically significant increase (p < 0.01). Based on the subscale index, the verbal comprehension index (VCI) and processing speed index (PSI) scores both showed a statistically significant increase from 100.6 to 106.75 and from 108.05 to 119.05 (p < 0.01), respectively. The PSI of the children included in the analysis showed a statistically significant increase compared to the historical control group. This study suggests that children who participate in Mahjong classes during their childhood have increased PSI scores of WISC-IV.
| S-EPMC9549265 | biostudies-literature
Project description:Genetic and epigenetic alterations in FK506-binding protein 5 ( FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD). Some of these common variants can increase the expression of FKBP5, the gene that encodes FKBP51. Excess FKBP51 promotes hypothalamic-pituitary-adrenal (HPA) axis dysregulation through altered glucocorticoid receptor (GR) signaling. Thus, we hypothesized that GR activity could be restored by perturbing FKBP51. Here, we screened 1280 pharmacologically active compounds and identified three compounds that rescued FKBP51-mediated suppression of GR activity without directly activating GR. One of the three compounds, benztropine mesylate, disrupted the association of FKBP51 with the GR/Hsp90 complex in vitro. Moreover, we show that removal of FKBP51 from this complex by benztropine restored GR localization in ex vivo brain slices and primary neurons from mice. In conclusion, we have identified a novel disruptor of the FKBP51/GR/Hsp90 complex. Targeting this complex may be a viable approach to developing treatments for disorders related to aberrant FKBP51 expression.
| S-EPMC6126901 | biostudies-literature
Project description:The neural substrate of high intelligence performances remains not well understood. Based on diffusion tensor imaging (DTI) which provides microstructural information of white matter fibers, we proposed in this work to investigate the relationship between structural brain connectivity and intelligence quotient (IQ) scores. Fifty-seven children (8-12 y.o.) underwent a MRI examination, including conventional T1-weighted and DTI sequences, and neuropsychological testing using the fourth edition of Wechsler Intelligence Scale for Children (WISC-IV), providing an estimation of the Full-Scale Intelligence Quotient (FSIQ) based on four subscales: verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI). Correlations between the IQ scores and both graphs and diffusivity metrics were explored. First, we found significant correlations between the increased integrity of WM fiber-bundles and high intelligence scores. Second, the graph theory analysis showed that integration and segregation graph metrics were positively and negatively correlated with WISC-IV scores, respectively. These results were mainly driven by significant correlations between FSIQ, VCI, and PRI and graph metrics in the temporal and parietal lobes. In conclusion, these findings demonstrated that intelligence performances are related to the integrity of WM fiber-bundles as well as the density and homogeneity of WM brain networks.
| S-EPMC7691327 | biostudies-literature
Project description:BackgroundCognitive impairment can complicate minor stroke, but there is limited information on risk factors including peak cognitive ability earlier in life.MethodsWe recruited patients with clinically-evident lacunar or minor non-lacunar ischaemic stroke, recorded clinical features, vascular risk factors, magnetic resonance imaging-detected stroke sub-type and small vessel disease burden. At 1-3 and 12 months after stroke, we assessed educational attainment (years of education), current cognition (Addenbrooke's Cognitive Examination-Revised), pre-morbid intelligence (National Adult Reading Test) and dependency (modified Rankin Scale).ResultsWe recruited 157 patients (87 lacunar, 64 non-lacunar ischaemic strokes), median age 66 (inter-quartile range 56-74) years, 36/157 (23%) patients had a Addenbrooke's Cognitive Examination-Revised score < 82 at one to three months, 29/151 (19%) had a Addenbrooke's Cognitive Examination-Revised < 82 at one year. Lower National Adult Reading Test score (cognitive impairment per point on National Adult Reading Test odds ratio 0.91, 95% confidence interval 0.87, 0.95) and older age (per year of age odds ratio 1.04 (95% confidence interval 1.01, 1.08) predicted one-year cognitive impairment more than stroke severity (per point on National Institute of Health Stroke Scale odds ratio 0.96 (95% confidence interval 0.0.68, 1.31)) or vascular risk factors e.g. hypertension (odds ratio for diagnosis of hypertension 0.52 (95% confidence interval 0.24, 1.15). Cognitive impairment was associated with having more white matter hyper-intensities (odds ratio per point increase in Fazekas score 1.42, 95% confidence interval 1.11, 1.83).DiscussionThis observational study provides evidence that pre-morbid intelligence quotient and education predict cognition after stroke, and confirms the association between cognitive impairment and small vessel disease.ConclusionPre-morbid intelligence should be considered in future studies of post-stroke cognition.
| S-EPMC6460404 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a 5-year survival rate of <8%. Its dismal prognosis stems from inefficient therapeutic modalities owing to the lack of understanding about pancreatic cancer pathogenesis. Considering the molecular complexity and heterogeneity of PDAC, identification of novel molecular contributors involved in PDAC onset and progression using global "omics" analysis will pave the way to improved strategies for disease prevention and therapeutic targeting. Meta-analysis of multiple miRNA microarray datasets containing healthy controls (HC), chronic pancreatitis (CP) and PDAC cases, identified 13 miRNAs involved in the progression of PDAC. These miRNAs showed dysregulation in both tissue as well as blood samples, along with progressive decrease in expression from HC to CP to PDAC. Gene-miRNA interaction analysis further elucidated 5 miRNAs (29a/b, 27a, 130b and 148a) that are significantly downregulated in conjunction with concomitant upregulation of their target genes throughout PDAC progression. Among these, miRNA-29a/b targeted genes were found to be most significantly altered in comparative profiling of HC, CP and PDAC, indicating its involvement in malignant evolution. Further, pathway analysis suggested direct involvement of miRNA-29a/b in downregulating the key pathways associated with PDAC development and metastasis including focal adhesion signaling and extracellular matrix organization. Our systems biology data analysis, in combination with real-time PCR validation indicates direct functional involvement of miRNA-29a in PDAC progression and is a potential prognostic marker and therapeutic candidate for patients with progressive disease.
| S-EPMC6333820 | biostudies-literature
Project description:Recent clinical studies indicate a strong link between AKI and progression of CKD. The increasing prevalence of AKI must compel the nephrology community to consider the long-term ramifications of this syndrome. Considerable gaps in knowledge exist regarding the connection between AKI and CKD. The 13th Acute Dialysis Quality Initiative meeting entitled "Therapeutic Targets of Human Acute Kidney Injury: Harmonizing Human and Experimental Animal Acute Kidney Injury" convened in April of 2014 and assigned a working group to focus on issues related to progression after AKI. This article provides a summary of the key conclusions and recommendations of the group, including an emphasis on terminology related to injury and repair processes for both clinical and preclinical studies, elucidation of pathophysiologic alterations of AKI, identification of potential treatment strategies, identification of patients predisposed to progression, and potential management strategies.
| S-EPMC4769207 | biostudies-literature
Project description:Intelligence quotient (IQ) testing is standard for evaluating cognitive abilities in genomic studies but requires professional expertise in administration and interpretation, and IQ scores do not translate into insights on implicated brain systems that can link genes to behavior. Individuals with 22q11.2 deletion syndrome (22q11.2DS) often undergo IQ testing to address special needs, but access to testing in resource-limited settings is challenging. The brief Penn Computerized Neurocognitive Battery (CNB) provides measures of cognitive abilities related to brain systems and can screen for cognitive dysfunction. To examine the relation between CNB measures and IQ, we evaluated participants with the 22q11.2DS from Philadelphia and Tel Aviv (N = 117; 52 females; mean age 18.8) who performed both an IQ test and the CNB with a maximum of 5 years between administrations and a subsample (n = 24) who had both IQ and CNB assessments at two time points. We estimated domain-level CNB scores using exploratory factor analysis (including bifactor for overall scores) and related those scores (intraclass correlations (ICCs)) to the IQ scores. We found that the overall CNB accuracy score showed similar correlations between time 1 and time 2 as IQ (0.775 for IQ and 0.721 for CNB accuracy), correlated well with the IQ scores (ICC = 0.565 and 0.593 for time 1 and time 2, respectively), and correlated similarly with adaptive functioning (0.165 and 0.172 for IQ and CNB, respectively). We provide a crosswalk (from linear equating) between standardized CNB and IQ scores. Results suggest that one can substitute the CNB for IQ testing in future genetic studies that aim to probe specific domains of brain-behavior relations beyond IQ.
| S-EPMC8413730 | biostudies-literature
Project description:Aim:We aimed to investigate the involvement of premorbid intelligence quotient in higher prevalence of smoking in patients with schizophrenia. Methods:Participants included 190 patients with schizophrenia (mean?±?standard deviation age: 37.7?±?10.8?years; 88 males and 102 females) and 312 healthy individuals (mean?±?standard deviation age: 38.1?±?13.8; 166 males and 146 females), matched for age, sex, and ethnicity (Japanese). Premorbid intelligence quotient was estimated using the Japanese Adult Reading Test and distress symptoms were assessed using the Hopkins Symptom Check List. Current smoking information was collected according to self-declarations. Results:As expected, the smoking rate was higher, while mean education level and Japanese Adult Reading Test scores were significantly lower, in patients with schizophrenia than in healthy individuals (p?<?0.01). The mean education level and Japanese Adult Reading Test scores were significantly lower in the smoker group than in the non-smoker group in both patients and healthy individuals (p?<?0.05). In the patient group alone, Hopkins Symptom Check List subscale and total scores were significantly higher in the smoker group than in the non-smoker group (p?<?0.05). A multivariate regression analysis showed that the Japanese Adult Reading Test score was a significant and negative predictor for smoking (p?<?0.001, odds ratio?=?0.97; 95% confidence interval: 0.96-0.99). Conclusion:Our results suggest that lower estimated premorbid intelligence quotient is an important variable in elucidating smoking behavior in humans and may be associated with higher prevalence of smoking in patients with schizophrenia.
| S-EPMC6176847 | biostudies-other