scholarly journals O11.4. INTERACTOME OVERLAP BETWEEN SCHIZOPHRENIA AND COGNITION

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S28-S28
Author(s):  
Elise Koch ◽  
Brin Rosenthale ◽  
Anders Lundquist ◽  
Chi-Hua Chen ◽  
Karolina Kauppi
Keyword(s):  
Cognitive Performance ◽  
Genetic Architecture ◽  
Cognitive Impairments ◽  
Long Term Potentiation ◽  
Pathway Enrichment Analysis ◽  
Healthy Individuals ◽  
Risk Genes ◽  
Interactome Network ◽  
Genetic Overlap ◽  
Network Space

Abstract Background Cognitive impairments constitute a core feature of schizophrenia, and a genetic overlap between schizophrenia and cognitive functioning in healthy individuals has been identified. However, due to the high polygenicity and complex genetic architecture of both traits, overlapping biological pathways have not yet been identified between schizophrenia and normal cognitive ability. Network medicine offers a framework to study biologically meaningful gene networks through protein-protein interactions among risk genes. Here, established network-based methods were used to further reveal the biological relatedness of schizophrenia and cognition. Methods The protein interactome was used to examine the genetic link between schizophrenia risk genes and genes associated with cognitive performance in healthy individuals. First, we used a method called network separation to examine if there is an overlap between schizophrenia and cognition in the interactome network space. Then, we used network propagation analyses to identify schizophrenia risk genes that are close to cognition-associated genes in the interactome network space. Gene ontology and pathway enrichment analysis was performed to describe the function of this gene set. Results Network separation analyses showed a profound interactome overlap between schizophrenia risk genes and genes associated with cognitive performance (SAB = -0.22, z-score = -6.80, p = 5.38e-12). We identified 140 schizophrenia risk genes that are close to cognition-associated genes in the interactome. Risk genes close to cognition were enriched for pathways including long-term potentiation and Alzheimer’s disease, and included genes with a role in neurotransmitter systems implemented in cognition, such as glutamate and dopamine, that were not part of the direct genetic overlap. Moreover, schizophrenia risk genes close to cognition included 45 druggable genes not yet used as drug targets. Discussion These results pinpoint schizophrenia risk genes of particular interest for further examination in schizophrenia patient groups to reveal the genetic architecture of cognitive impairments in schizophrenia, of which some are druggable genes with potential as candidate targets for cognitive enhancing drugs.

Identification of novel cardiovascular disease associated metabolites using untargeted metabolomics

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shams Tabrez ◽  
Mohammed Razeeth Shait Mohammed ◽  
Nasimudeen R. Jabir ◽  
Mohammad Imran Khan
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Pathways ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Healthy Individuals ◽  
Great Opportunity ◽  
Pathway Enrichment ◽  
Pathophysiological Role ◽  
The World ◽  
Metabolomic Approach

Abstract Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality around the world. Early diagnosis of CVD could provide the opportunity for sensible management and better clinical outcome along with the prevention of further progression of the disease. In the current study, we used an untargeted metabolomic approach to identify possible metabolite(s) that associate well with the CVD and could serve either as therapeutic target or disease-associated metabolite. We identified 26 rationally adjusted unique metabolites that were differentially present in the serum of CVD patients compared with healthy individuals, among them 15 were found to be statistically significant. Out of these metabolites, we identified some novel metabolites like UDP-l-rhamnose and N1-acetylspermidine that have not been reported to be linked with CVD directly. Further, we also found that some metabolites like ethanolamide, solanidine, dimethylarginine, N-acetyl-l-tyrosine, can act as a discriminator of CVD. Metabolites integrating pathway enrichment analysis showed enrichment of various important metabolic pathways like histidine metabolism, methyl histidine metabolism, carnitine synthesis, along with arginine and proline metabolism in CVD patients. Our study provides a great opportunity to understand the pathophysiological role and impact of the identified unique metabolites and can be extrapolated as specific CVD specific metabolites.

scholarly journals Genetic markers of ADHD-related variations in intracranial volume

2017 ◽  
Author(s):  
Marieke Klein ◽  
Raymond K. Walters ◽  
Ditte Demontis ◽  
Jason L. Stein ◽  
Derrek P. Hibar ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Meta Analysis ◽  
Neurodevelopmental Disorder ◽  
Structure And Function ◽  
Intracranial Volume ◽  
Biological Mechanisms ◽  
Brain Volumes ◽  
Hyperactivity Disorder ◽  
Genetic Overlap ◽  
And Function

ABSTRACTAttention-Deficit/Hyperactivity Disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with a complex pathophysiology, where genetic risk is hypothesized to be mediated by alterations in structure and function of diverse brain networks. We tested one aspect of this hypothesis by investigating the genetic overlap between ADHD (n=55,374) and (mainly subcortical) brain volumes (n=11,221-24,704), using the largest publicly available studies. At the level of common variant genetic architecture, we discovered a significant negative genetic correlation between ADHD and intracranial volume (ICV). Meta-analysis of individual variants found significant loci associated with both ADHD risk and ICV; additional loci were identified for ADHD and amygdala, caudate nucleus, and putamen volumes. Gene-set analysis in the ADHD-ICV meta-analytic data showed significant association with variation in neurite outgrowth-related genes. In summary, our results suggest new hypotheses about biological mechanisms involved in ADHD etiology and highlight the need to study additional brain parameters.

EXPOSURE TO AIR POLLUTION AND COGNITIVE PERFORMANCE OF HEALTHY INDIVIDUALS AT RISK FOR ALZHEIMER’S DISEASE

2017 ◽  
Vol 13 (7) ◽  
pp. P564-P565
Author(s):  
Gonzalo Sánchez-Benavides ◽  
Mireia Gascón ◽  
Nina Gramunt ◽  
Xavier Gotsens ◽  
Karine Fauria ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Air Pollution ◽  
Cognitive Performance ◽  
Healthy Individuals

scholarly journals The Alzheimer’s comorbidity phenome: mining from a large patient database and phenome-driven genetics prediction

JAMIA Open ◽  
2018 ◽  
Vol 2 (1) ◽  
pp. 131-138 ◽  
Author(s):  
Chunlei Zheng ◽  
Rong Xu
Keyword(s):  
Large Scale ◽  
Neurodegenerative Disorder ◽  
Association Studies ◽  
Characteristic Curve ◽  
Adverse Event Reporting System ◽  
Public Health Problem ◽  
Pathway Enrichment Analysis ◽  
Ranking Algorithm ◽  
Risk Genes ◽  
Large Patient

Abstract Objective Alzheimer’s disease (AD) is a severe neurodegenerative disorder and has become a global public health problem. Intensive research has been conducted for AD. But the pathophysiology of AD is still not elucidated. Disease comorbidity often associates diseases with overlapping patterns of genetic markers. This may inform a common etiology and suggest essential protein targets. US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collects large-scale postmarketing surveillance data that provide a unique opportunity to investigate disease co-occurrence pattern. We aim to construct a heterogeneous network that integrates disease comorbidity network (DCN) from FAERS with protein–protein interaction (PPI) to prioritize the AD risk genes using network-based ranking algorithm. Materials and Methods We built a DCN based on indication data from FAERS using association rule mining. DCN was further integrated with PPI network. We used random walk with restart ranking algorithm to prioritize AD risk genes. Results We evaluated the performance of our approach using AD risk genes curated from genetic association studies. Our approach achieved an area under a receiver operating characteristic curve of 0.770. Top 500 ranked genes achieved 5.53-fold enrichment for known AD risk genes as compared to random expectation. Pathway enrichment analysis using top-ranked genes revealed that two novel pathways, ERBB and coagulation pathways, might be involved in AD pathogenesis. Conclusion We innovatively leveraged FAERS, a comprehensive data resource for FDA postmarket drug safety surveillance, for large-scale AD comorbidity mining. This exploratory study demonstrated the potential of disease-comorbidities mining from FAERS in AD genetics discovery.

scholarly journals The Effectiveness of Exercise on Cognitive Performance in Individuals with Known Vascular Disease: A Systematic Review

2019 ◽  
Vol 8 (3) ◽  
pp. 294 ◽  
Author(s):  
Alyssa Brunt ◽  
David Albines ◽  
Diana Hopkins-Rosseel
Keyword(s):  
Systematic Review ◽  
Resistance Training ◽  
Vascular Disease ◽  
Cognitive Performance ◽  
Dose Response ◽  
Cognitive Impairments ◽  
Positive Association ◽  
Cardiovascular Fitness ◽  
Healthy Elderly ◽  
Increased Risk

Patients with known vascular disease are at increased risk for cognitive impairments. Exercise has been shown to improve cognition in healthy elderly populations and those with mild cognitive impairments. We explored the literature to understand exercise as a modality to improve cognition in those with vascular disease, focusing on dose-responses. A systematic review was conducted through 2017 using Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Ovid Embase, and Ovid MEDLINE databases. Eligible studies examined effects of exercise on memory and cognition in cardiovascular (CVD) or cerebrovascular disease (CBVD). Data extracted included group characteristics, exercise dosage and outcomes measures employed. Twenty-two studies (12 CVD, 10 CBVD) met the inclusion criteria. Interventions included aerobic, resistance, or mixed training, with neuropsychological test batteries assessing cognition. In CVD populations, five studies demonstrated improved cardiovascular fitness and cognition with aerobic training, and another seven studies suggested a dose-response. In CBVD trials, four studies reported improved cognition, with no effects observed in the fifth study. Another study found enhanced cognition with resistance training and four demonstrated a positive association between functional capacity and cognition following combined aerobic and resistance training. Exercise is able to positively affect cognitive performance in those with known vascular disease. There is evidence to suggest a dose–response relationship. Further research is required to optimize prescription.

scholarly journals Effect of Sugar versus Mixed Breakfast on Metabolic and Neurofunctional Responses in Healthy Individuals

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Roberto Codella ◽  
Stefano Benedini ◽  
Stefano Paini ◽  
Andrea Caumo ◽  
Michela Adamo ◽  
...  
Keyword(s):  
Evoked Potentials ◽  
Cognitive Performance ◽  
Cognitive Processing ◽  
Sensory Information ◽  
Crossover Design ◽  
P300 Latency ◽  
Healthy Individuals ◽  
Ghrelin Concentration ◽  
Insulinemic Response ◽  
Plasma Ghrelin Concentration

We investigated the effects of glucose and diverse breakfasts on glucose increment and ghrelin suppression and cognitive processing of sensory information assessed by frontal P300 evoked potentials. In a randomized crossover design, 12 healthy individuals (6M/6F; BMI 22.2 ± 0.4 kg/m2; 27 ± 1.3 years, mean ± SEM) underwent 50 g OGTT (A) and 3 breakfasts (B1: milk and cereals; B2: milk, apple, and chocolate cream-filled sponge cake; B3: milk, apple, bread, and hazelnut chocolate cream) to assess plasma glucose-, insulin-, and ghrelin excursions. An electroencephalography was performed before and 100 min after consumption of each load to measure the latency of frontal P300 evoked potentials as index of cognitive performance. Breakfasts B1 and B2 exhibited significantly lower glycemic and insulinemic responses as compared to A. Breakfast B3 exhibited significantly lower glycemic, but not insulinemic response, as compared to A. Final plasma ghrelin inhibition was more pronounced, albeit not significantly, in all breakfasts with respect to A. P300 latency tended to decrease following each of the three breakfasts, but B3 was the only breakfast capable to elicit a statistically significant reduction in P300 latency with respect to A (p<0.01), suggesting ameliorated cognitive performance. Such amelioration was correlated with the 2-hour final inhibition of plasma ghrelin concentration (r=0.61,p=0.01).

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