scholarly journals Body mass variations relate to fractionated functional brain hierarchies

2020 ◽  
Author(s):  
Bo-yong Park ◽  
Hyunjin Park ◽  
Filip Morys ◽  
Mansu Kim ◽  
Kyoungseob Byeon ◽  
...  
Keyword(s):  
Young Adults ◽  
Body Mass ◽  
Cell Types ◽  
Modular Architecture ◽  
Brain Organization ◽  
Functional Connectome ◽  
Genome Wide ◽  
Learning Techniques ◽  
Connectivity Patterns ◽  
Cerebellar Cell

AbstractVariations in body mass index (BMI) have been suggested to relate to atypical brain organization, yet connectome-level substrates of BMI and their neurobiological underpinnings remain unclear. Studying 325 healthy young adults, we examined association between functional connectome organization and BMI variations. We capitalized on connectome manifold learning techniques, which represent macroscale functional connectivity patterns along continuous hierarchical axes that dissociate low level and higher order brain systems. We observed an increased differentiation between unimodal and heteromodal association networks in individuals with higher BMI, indicative of an increasingly segregated modular architecture and a disruption in the hierarchical integration of different brain system. Transcriptomic decoding and subsequent gene enrichment analyses identified genes previously implicated in genome-wide associations to BMI and specific cortical, striatal, and cerebellar cell types. These findings provide novel insights for functional connectome substrates of BMI variations in healthy young adults and point to potential molecular associations.

scholarly journals Inter-individual body mass variations relate to fractionated functional brain hierarchies

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Bo-yong Park ◽  
Hyunjin Park ◽  
Filip Morys ◽  
Mansu Kim ◽  
Kyoungseob Byeon ◽  
...  
Keyword(s):  
Young Adults ◽  
Body Mass ◽  
Functional Organization ◽  
Cell Types ◽  
Modular Architecture ◽  
Brain Organization ◽  
Genome Wide ◽  
Learning Techniques ◽  
Cerebellar Cell ◽  
The Brain

AbstractVariations in body mass index (BMI) have been suggested to relate to atypical brain organization, yet connectome-level substrates of BMI and their neurobiological underpinnings remain unclear. Studying 325 healthy young adults, we examined associations between functional connectivity and inter-individual BMI variations. We utilized non-linear connectome manifold learning techniques to represent macroscale functional organization along continuous hierarchical axes that dissociate low level and higher order brain systems. We observed an increased differentiation between unimodal and heteromodal association networks in individuals with higher BMI, indicative of a disrupted modular architecture and hierarchy of the brain. Transcriptomic decoding and gene enrichment analyses identified genes previously implicated in genome-wide associations to BMI and specific cortical, striatal, and cerebellar cell types. These findings illustrate functional connectome substrates of BMI variations in healthy young adults and point to potential molecular associations.

scholarly journals Specification of diverse cell types during early neurogenesis of the mouse cerebellum

2018 ◽  
Author(s):  
John W. Wizeman ◽  
Qiuxia Guo ◽  
Elliot Wilion ◽  
James Y.H. Li
Keyword(s):  
Cell Fate ◽  
Developmental Trajectories ◽  
Ventricular Zone ◽  
Cell Types ◽  
Genome Wide ◽  
Integral Role ◽  
Cerebellar Cell ◽  
Early Neurogenesis ◽  
And Function ◽  
Developing Cerebellum

SUMMARYWe applied single-cell RNA sequencing to profile genome-wide gene expression in about 9,400 individual cerebellar cells from the mouse embryo at embryonic day 13.5. Reiterative clustering identified the major cerebellar cell types and subpopulations of different lineages. Through pseudotemporal ordering to reconstruct developmental trajectories, we identified novel transcriptional programs controlling cell fate specification of populations arising from the ventricular zone and the anterior rhombic lip, two distinct germinal zones of the embryonic cerebellum. Together, our data revealed cell-specific markers for studying the cerebellum, important specification decisions, and a number of previously unknown subpopulations that may play an integral role in the formation and function of the cerebellum. Importantly, we identified a potential mechanism of vermis formation, which is affected by multiple congenital cerebellar defects. Our findings will facilitate new discovery by providing insights into the molecular and cell type diversity in the developing cerebellum.

Body Mass Index and Memory Function in Young Adults

2014 ◽  
Author(s):  
Mitchell Metzger ◽  
Morgan Myers ◽  
Emily Embrescia ◽  
David F. Vanata
Keyword(s):  
Body Mass Index ◽  
Young Adults ◽  
Body Mass ◽  
Memory Function

scholarly journals Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types

2021 ◽  
Vol 7 (3) ◽  
pp. eabd9036
Author(s):  
Sara Saez-Atienzar ◽  
Sara Bandres-Ciga ◽  
Rebekah G. Langston ◽  
Jonggeol J. Kim ◽  
Shing Wan Choi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Data Driven Approach ◽  
Single Nucleus ◽  
Lateral Sclerosis

Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated six differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, MAPKAPK3, PLXNB2, and SCFD1) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types.

scholarly journals The genetic architecture of structural left–right asymmetry of the human brain

2021 ◽  
Author(s):  
Zhiqiang Sha ◽  
Dick Schijven ◽  
Amaia Carrion-Castillo ◽  
Marc Joliot ◽  
Bernard Mazoyer ◽  
...  
Keyword(s):  
Brain Asymmetry ◽  
Functional Enrichment ◽  
Brain Organization ◽  
Genome Wide ◽  
Brain Expression ◽  
Using Data ◽  
Left Right Asymmetry ◽  
The Uk ◽  
Subcortical Volume

AbstractLeft–right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and it can be altered in cognitive and psychiatric disorders. No mechanism has yet been identified for establishing the human brain’s left–right axis. We performed multivariate genome-wide association scanning of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci associated with different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left–right axis determination in other organs of invertebrates and frogs. Genetic variants associated with brain asymmetry overlapped with those associated with autism, educational attainment and schizophrenia. Comparably large datasets will likely be required in future studies, to replicate and further clarify the associations of microtubule-related genes with variation in brain asymmetry, behavioural and psychiatric traits.

scholarly journals AKT Alters Genome-Wide Estrogen Receptor α Binding and Impacts Estrogen Signaling in Breast Cancer

2008 ◽  
Vol 28 (24) ◽  
pp. 7487-7503 ◽  
Author(s):  
Poornima Bhat-Nakshatri ◽  
Guohua Wang ◽  
Hitesh Appaiah ◽  
Nikhil Luktuke ◽  
Jason S. Carroll ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Binding Sites ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Primary Tumors ◽  
Genome Wide ◽  
Extracellular Signal

ABSTRACT Estrogen regulates several biological processes through estrogen receptor α (ERα) and ERβ. ERα-estrogen signaling is additionally controlled by extracellular signal activated kinases such as AKT. In this study, we analyzed the effect of AKT on genome-wide ERα binding in MCF-7 breast cancer cells. Parental and AKT-overexpressing cells displayed 4,349 and 4,359 ERα binding sites, respectively, with ∼60% overlap. In both cell types, ∼40% of estrogen-regulated genes associate with ERα binding sites; a similar percentage of estrogen-regulated genes are differentially expressed in two cell types. Based on pathway analysis, these differentially estrogen-regulated genes are linked to transforming growth factor β (TGF-β), NF-κB, and E2F pathways. Consistent with this, the two cell types responded differently to TGF-β treatment: parental cells, but not AKT-overexpressing cells, required estrogen to overcome growth inhibition. Combining the ERα DNA-binding pattern with gene expression data from primary tumors revealed specific effects of AKT on ERα binding and estrogen-regulated expression of genes that define prognostic subgroups and tamoxifen sensitivity of ERα-positive breast cancer. These results suggest a unique role of AKT in modulating estrogen signaling in ERα-positive breast cancers and highlights how extracellular signal activated kinases can change the landscape of transcription factor binding to the genome.

A genomewide study of body mass index and its genetic correlation with thromboembolic risk

2014 ◽  
Vol 112 (11) ◽  
pp. 1036-1043 ◽  
Author(s):  
Geórgia Pena ◽  
Andrey Ziyatdinov ◽  
Alfonso Buil ◽  
Sonia López ◽  
Jordi Fontcuberta ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Genetic Correlation ◽  
Body Mass ◽  
Thromboembolic Disease ◽  
Thromboembolic Risk ◽  
Genetic Components ◽  
Genome Wide ◽  
Thrombosis Risk ◽  
Bivariate Linkage Analysis ◽  
Genome Wide Scan

SummaryThrombosis and obesity are complex epidemiologically associated diseases. The mechanism of this association is not yet understood. It was the objective of this study to identify genetic components of body mass index (BMI) and their possible role in the risk of thromboembolic disease. With the self-reported BMI of 397 individuals from 21 extended families enrolled in the GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project, we estimated the heritability of BMI and the genetic correlation with the risk of thrombosis. Subjects were genotyped for an autosomal genome-wide scan with 363 highly-informative DNA markers. Univariate and bivariate multipoint linkage analyses were performed. The heritability for BMI was 0.31 (p= 2.9×10–5). Thromboembolic disease (including venous and arterial) and BMI had a significant genetic correlation (ρG= 0.54, p= 0.005). Two linkage signals for BMI were obtained, one at 13q34 (LOD= 3.36, p= 0.0004) and other at 2q34, highly suggestive of linkage (LOD= 1.95). Bivariate linkage analysis with BMI and thrombosis risk also showed a significant signal at 13q34 (LOD= 3), indicating that this locus influences at the same time normal variation in the BMI phenotype as well as susceptibility to thrombosis. In conclusion, BMI and thrombosis are genetically correlated. The locus 13q34, which showed pleiotropy with both phenotypes, contains two candidate genes, which may explain our linkage pleiotropic signal and deserve further investigation as possible risk factors for obesity and thrombosis.

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