scholarly journals Astrocytes in schizophrenia

2021 ◽  
Vol 5 ◽  
pp. 239821282110091
Author(s):  
Tina Notter
Keyword(s):  
Mental Disorder ◽  
Glial Cells ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Current Evidence ◽  
Experimental Investigations ◽  
Research Areas ◽  
Neuronal Signalling ◽  
Health And Disease ◽  
Abnormal Brain

Schizophrenia is a severe and clinically heterogenous mental disorder affecting approximately 1% of the population worldwide. Despite tremendous achievements in the field of schizophrenia research, its precise aetiology remains elusive. Besides dysfunctional neuronal signalling, the pathophysiology of schizophrenia appears to involve molecular and functional abnormalities in glial cells, including astrocytes. This article provides a concise overview of the current evidence supporting altered astrocyte activity in schizophrenia, which ranges from findings obtained from post-mortem immunohistochemical analyses, genetic association studies and transcriptomic investigations, as well as from experimental investigations of astrocyte functions in animal models. Integrating the existing data from these research areas strongly suggests that astrocytes have the capacity to critically affect key neurodevelopmental and homeostatic processes pertaining to schizophrenia pathogenesis, including glutamatergic signalling, synaptogenesis, synaptic pruning and myelination. The further elucidation of astrocytes functions in health and disease may, therefore, offer new insights into how these glial cells contribute to abnormal brain development and functioning underlying this debilitating mental disorder.

Genomic Variations and Susceptibility to Sepsis

2006 ◽  
Vol 17 (4) ◽  
pp. 394-422 ◽  
Author(s):  
Elizabeth D. E. Papathanassoglou ◽  
Margarita D. Giannakopoulou ◽  
Evangelos Bozas
Keyword(s):  
Intracellular Signaling ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Genetic Variations ◽  
Adverse Outcomes ◽  
Current Evidence ◽  
Genomic Variations ◽  
Individualized Care ◽  
Study Results ◽  
Shock Proteins

The considerable variability in septic patients’ outcomes, which exceeds our understanding of the pathophysiology of sepsis and defies our current prognostic tools, has prompted investigation in the genetic variations that may predispose individuals for increased susceptibility to sepsis and adverse outcomes. This article aims to critically review current evidence from genetic association studies regarding the role of genetic polymorphisms in sepsis. Findings regarding polymorphisms in intercellular messenger mediators (cytokines), membrane-bound inflammatory receptors, intracellular signaling cascades, heat shock proteins, coagulation/fibrinolysis pathways, apoptotic mechanisms, and neuroendocrine axes are presented and discussed. Study results are often discrepant, whereas many methodological limitations, in terms of both study design and genotyping methods, may render the results difficult to generalize. Nonetheless, a role for genomic variations in sepsis outcomes has emerged. A theoretical framework for incorporation of genetic variations into individualized care planning based on complexity theory is proposed, and future prospects of microarray technology and systems modelling are discussed briefly.

scholarly journals Latin American Genes: The Great Forgotten in Rheumatoid Arthritis

2020 ◽  
Vol 10 (4) ◽  
pp. 196 ◽  
Author(s):  
Roberto Díaz-Peña ◽  
Luis A. Quiñones ◽  
Patricia Castro-Santos ◽  
Josefina Durán ◽  
Alejandro Lucia
Keyword(s):  
Rheumatoid Arthritis ◽  
Personalized Medicine ◽  
Latin American ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Targeted Prevention ◽  
Successful Implementation ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Health And Disease

The successful implementation of personalized medicine will rely on the integration of information obtained at the level of populations with the specific biological, genetic, and clinical characteristics of an individual. However, because genome-wide association studies tend to focus on populations of European descent, there is a wide gap to bridge between Caucasian and non-Caucasian populations before personalized medicine can be fully implemented, and rheumatoid arthritis (RA) is not an exception. In this review, we discuss advances in our understanding of genetic determinants of RA risk among global populations, with a focus on the Latin American population. Geographically restricted genetic diversity may have important implications for health and disease that will remain unknown until genetic association studies have been extended to include Latin American and other currently under-represented ancestries. The next few years will witness many breakthroughs in personalized medicine, including applications for common diseases and risk stratification instruments for targeted prevention/intervention strategies. Not all of these applications may be extrapolated from the Caucasian experience to Latin American or other under-represented populations.

scholarly journals Targeting the Renin–Angiotensin–Aldosterone System to Prevent Hypertension and Kidney Disease of Developmental Origins

2021 ◽  
Vol 22 (5) ◽  
pp. 2298
Author(s):  
Chien-Ning Hsu ◽  
You-Lin Tain
Keyword(s):  
Kidney Disease ◽  
Current Knowledge ◽  
Current Evidence ◽  
Developmental Origins ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Health And Disease ◽  
Nitric Oxide Deficiency ◽  
Developing Kidney ◽  
Prevention Of Hypertension

The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease. The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood. This theory is known as developmental origins of health and disease (DOHaD). Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming. In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins. To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.

scholarly journals Case–Parent Trio Studies in Cleft Lip and Palate

2020 ◽  
Vol 07 (03) ◽  
pp. 075-079
Author(s):  
Mahamad Irfanulla Khan ◽  
Prashanth CS
Keyword(s):  
Genetic Variants ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Association Studies ◽  
Geographical Location ◽  
Genetic Association Studies ◽  
Population Based ◽  
Genome Wide Association Studies ◽  
Family Based ◽  
Study Designs

AbstractCleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans involving various genetic and environmental risk factors. The prevalence of CL/P varies according to geographical location, ethnicity, race, gender, and socioeconomic status, affecting approximately 1 in 800 live births worldwide. Genetic studies aim to understand the mechanisms contributory to a phenotype by measuring the association between genetic variants and also between genetic variants and phenotype population. Genome-wide association studies are standard tools used to discover genetic loci related to a trait of interest. Genetic association studies are generally divided into two main design types: population-based studies and family-based studies. The epidemiological population-based studies comprise unrelated individuals that directly compare the frequency of genetic variants between (usually independent) cases and controls. The alternative to population-based studies (case–control designs) includes various family-based study designs that comprise related individuals. An example of such a study is a case–parent trio design study, which is commonly employed in genetics to identify the variants underlying complex human disease where transmission of alleles from parents to offspring is studied. This article describes the fundamentals of case–parent trio study, trio design and its significances, statistical methods, and limitations of the trio studies.

scholarly journals Fine scale human genetic structure in three regions of Cameroon reveals episodic diversifying selection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin K. Esoh ◽  
Tobias O. Apinjoh ◽  
Steven G. Nyanjom ◽  
Ambroise Wonkam ◽  
Emile R. Chimusa ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Ethnic Groups ◽  
Genetic Association ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Genomic Region ◽  
Sub Saharan Africa ◽  
Genome Wide Association Studies ◽  
Fine Scale ◽  
Sub Saharan

AbstractInferences from genetic association studies rely largely on the definition and description of the underlying populations that highlight their genetic similarities and differences. The clustering of human populations into subgroups (population structure) can significantly confound disease associations. This study investigated the fine-scale genetic structure within Cameroon that may underlie disparities observed with Cameroonian ethnicities in malaria genome-wide association studies in sub-Saharan Africa. Genotype data of 1073 individuals from three regions and three ethnic groups in Cameroon were analyzed using measures of genetic proximity to ascertain fine-scale genetic structure. Model-based clustering revealed distinct ancestral proportions among the Bantu, Semi-Bantu and Foulbe ethnic groups, while haplotype-based coancestry estimation revealed possible longstanding and ongoing sympatric differentiation among individuals of the Foulbe ethnic group, and their Bantu and Semi-Bantu counterparts. A genome scan found strong selection signatures in the HLA gene region, confirming longstanding knowledge of natural selection on this genomic region in African populations following immense disease pressure. Signatures of selection were also observed in the HBB gene cluster, a genomic region known to be under strong balancing selection in sub-Saharan Africa due to its co-evolution with malaria. This study further supports the role of evolution in shaping genomes of Cameroonian populations and reveals fine-scale hierarchical structure among and within Cameroonian ethnicities that may impact genetic association studies in the country.

scholarly journals A SNaPshot Assay for Determination of the Mannose-Binding Lectin Gene Variants and an Algorithm for Calculation of Haplogenotype Combinations

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 301
Author(s):  
Jana Mrazkova ◽  
Petr Sistek ◽  
Jan Lochman ◽  
Lydie Izakovicova Holla ◽  
Zdenek Danek ◽  
...  
Keyword(s):  
Association Studies ◽  
Genetic Association Studies ◽  
Cost Effective ◽  
European Population ◽  
Mannose Binding Lectin ◽  
Nucleotide Polymorphisms ◽  
Online Application ◽  
Czech Population ◽  
Mannose Binding ◽  
Binding Lectin

Mannose-binding lectin (MBL) deficiency caused by the variability in the MBL2 gene is responsible for the susceptibility to and severity of various infectious and autoimmune diseases. A combination of six single nucleotide polymorphisms (SNPs) has a major impact on MBL levels in circulation. The aim of this study is to design and validate a sensitive and economical method for determining MBL2 haplogenotypes. The SNaPshot assay is designed and optimized to genotype six SNPs (rs1800451, rs1800450, rs5030737, rs7095891, rs7096206, rs11003125) and is validated by comparing results with Sanger sequencing. Additionally, an algorithm for online calculation of haplogenotype combinations from the determined genotypes is developed. Three hundred and twenty-eight DNA samples from healthy individuals from the Czech population are genotyped. Minor allele frequencies (MAFs) in the Czech population are in accordance with those present in the European population. The SNaPshot assay for MBL2 genotyping is a high-throughput, cost-effective technique that can be used in further genetic-association studies or in clinical practice. Moreover, a freely available online application for the calculation of haplogenotypes from SNPs is developed within the scope of this project.

scholarly journals Evaluation of genome-wide power of genetic association studies based on empirical data from the HapMap project

2007 ◽  
Vol 16 (20) ◽  
pp. 2494-2505 ◽  
Author(s):  
Yasuhito Nannya ◽  
Kenjiro Taura ◽  
Mineo Kurokawa ◽  
Shigeru Chiba ◽  
Seishi Ogawa
Keyword(s):  
Genetic Association ◽  
Empirical Data ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Hapmap Project ◽  
Genome Wide

scholarly journals Clinical, biochemical and genetic risk factors for 30-day and 5-year mortality in 518 adult patients subjected to cardiopulmonary bypass during cardiac surgery - the INFLACOR study.

2018 ◽  
Vol 65 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Maciej Michał Kowalik ◽  
Romuald Lango ◽  
Piotr Siondalski ◽  
Magdalena Chmara ◽  
Maciej Brzeziński ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Genetic Association ◽  
Biochemical Parameters ◽  
Cox Regression ◽  
Association Studies ◽  
Nyha Class ◽  
Genetic Association Studies ◽  
Chronic Obstructive

There is increasing evidence that genetic variability influence patients’ early morbidity after cardiac surgery performed using cardiopulmonary bypass (CPB). The use of mortality as an outcome measure in cardiac surgical genetic association studies is rare. We publish the 30-day and 5-year survival analyses with focus on pre-, intra-, postoperative variables, biochemical parameters, and genetic variants in the INFLACOR (INFlAmmation in Cardiac OpeRations) cohort.In a series of prospectively recruited 518 adult Polish Caucasians who underwent cardiac surgery in which CPB was used, the clinical data, biochemical parameters, IL-6, soluble ICAM-1, TNFa, soluble E-selectin, and 10 single nucleotide polymorphisms were evaluated for their associations with 30-day and 5-year mortality.The 30-day mortality was associated with: pre-operative prothrombin international normalized ratio, intra-operative blood lactate, postoperative serum creatine phosphokinase, and acute kidney injury requiring renal replacement therapy (AKI-RRT) in logistic regression. Factors that determined the 5-year survival included: pre-operative NYHA class, history of peripheral artery disease and severe chronic obstructive pulmonary disease, intra-operative blood transfusion; and postoperative peripheral hypothermia, myocardial infarction, infection, and AKI-RRT in Cox regression. The serum levels of IL-6 and ICAM-1 measured three hours after operation were associated with 30-day and 5-year mortality, respectively. The ICAM1 rs5498 was associated with 30-day and 5-year survival with borderline significance.Different risk factors determined the early (30-day) and late (5-year) survival after adult cardiac surgery in which cardiopulmonary bypass was used. Future genetic association studies in cardiac surgical patients should adjust for the identified chronic and acute postoperative risk factors.

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