Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Pay for performance - panacea or Pandora's box? Revisiting an old debate in the current economic environment

New research in neuroeconomics suggests that money may be a more powerful motivator than previously thought, with important implications for incentive pay programs

Intestinal intermediate filament polypeptides in C. elegans: Common and isotype-specific contributions to intestinal ultrastructure and function

The abundance and diversity of intermediate filaments (IFs) in the C. elegans intestine indicate important contributions to intestinal function and organismal wellbeing. Fluorescent IF reporters localize below the actin-rich brush border and are highly enriched in the lumen-enveloping endotube, which is attached to the C. elegans apical junction. Mapping intestinal viscoelasticity by contact-free Brillouin microscopy reveals that the IF-rich endotube is positioned at the interface between the stiff brush border and soft cytoplasm suggesting a mechanical buffering function to deal with the frequent luminal distortions occurring during food intake and movement. In accordance, depletion of IFB-2, IFC-2 and IFD-2 leads to intestinal lumen dilation although depletion of IFC-1, IFD-1 and IFP-1 do not. Ultrastructural analyses of loss of function mutants further show that IFC-2 mutants have a rarefied endotube and IFB-2 mutants lack an endotube altogether. Remarkably, almost all IFB-2- and IFC-2-deficient animals develop to fertile adults. But developmental retardation, reduced brood size, altered survival and increased sensitivity to microbial toxin, osmotic and oxidative stress are seen in both mutants albeit to different degrees. Taken together, we propose that individual intestinal IF polypeptides contribute in different ways to endotube morphogenesis and cooperate to cope with changing environments

Les microARN comme marqueurs périphériques précoces de l’inflammation et du statut nutritionnel des vaches laitières en début de lactation

Champ thématique : ProductionLes microARN sont des petits ARN non codants qui contrôlent divers processus biologiques dont la réponse immunitaire et le métabolisme. Chez les ruminants, les données sur les microARN augmentent rapidement. Ainsi, un séquençage haut débit de l’ensemble des microARN (collaboration avec l’Unité Gabi-Jouy) a permis d’établir un répertoire exhaustif (miRNome) dans la glande mammaire de vaches1 et de chèvres2 en lactation. De plus, notre étude portant sur la régulation nutritionnelle de leur expression dans la glande mammaire a mis en exergue 30 microARN régulés par la restriction alimentaire chez la chèvre en lactation3. Récemment, des microARN ont été décrits, chez l’homme, comme biomarqueurs de maladies humaines4 (Ribeiro & Sousa, 2014) alors que chez les animaux d’élevage, leur utilisation comme biomarqueur reste peu exploré. L’objectif de ce projet est de rechercher parmi les microARN présents dans les fluides (sang et/ou lait), des marqueurs précoces de l’inflammation ou de changements d'état nutritionnel, en exploitant le protocole expérimental mis en place dans le cadre du programme Ruminflame afin de les utiliser comme indicateurs de l’état physiologique ou pathologique des animaux

Les microARN comme marqueurs périphériques précoces de l’inflammation et du statut nutritionnel des vaches laitières en début de lactation

Champ thématique : ProductionLes microARN sont des petits ARN non codants qui contrôlent divers processus biologiques dont la réponse immunitaire et le métabolisme. Chez les ruminants, les données sur les microARN augmentent rapidement. Ainsi, un séquençage haut débit de l’ensemble des microARN (collaboration avec l’Unité Gabi-Jouy) a permis d’établir un répertoire exhaustif (miRNome) dans la glande mammaire de vaches1 et de chèvres2 en lactation. De plus, notre étude portant sur la régulation nutritionnelle de leur expression dans la glande mammaire a mis en exergue 30 microARN régulés par la restriction alimentaire chez la chèvre en lactation3. Récemment, des microARN ont été décrits, chez l’homme, comme biomarqueurs de maladies humaines4 (Ribeiro & Sousa, 2014) alors que chez les animaux d’élevage, leur utilisation comme biomarqueur reste peu exploré. L’objectif de ce projet est de rechercher parmi les microARN présents dans les fluides (sang et/ou lait), des marqueurs précoces de l’inflammation ou de changements d'état nutritionnel, en exploitant le protocole expérimental mis en place dans le cadre du programme Ruminflame afin de les utiliser comme indicateurs de l’état physiologique ou pathologique des animaux

Les globules gras comme source non-invasive de microARN mammaires

Les globules gras comme source non-invasive de microARN mammaires. 23. Rencontres autour des Recherches sur les Ruminant

Different miRNA contents between mammary epithelial cells and milk fat globules: a random or a targeted process?

International audienceMicroRNAs (miRNAs) are small noncoding RNAs present in milk-derived extracellular vesicles and milk fat globules (MFG). Nucleic acid content between the lactating mammary tissue (MT) and MFG are quite similar but discrepancies exist in their miRNA content. Our objective was to identify the origin of these discrepancies, and to evaluate the existence of a possible mechanism sorting miRNAs that will or will not be exported from the mammary epithelial cells (MECs) in bovine MFG.miR-125b-5p,miR-126-3p,miR-141-3p, andmiR-204-5p, chosen on the basis of their abundance in the MT, were quantified using RT-qPCR in lactating cow MT, MFG, and laser capture-microdissected MECs. Two miRNAs (miR-125b-5pandmiR-141-3p) were detected in the MT as well as in MFG and MECs.miR-204-5pwas detected only in the MT, suggesting that it is very likely expressed in a cell type other than MECs.miR-126-3pwas detected both in the MT and in MECs but not in MFG, suggesting a targeting mechanism for miRNAs in MECs. These results highlights differences in miRNA content between MECs and MFG may be due to a possibly not random mechanism for loading MFG with miRNA cargos that could involve a variable distribution in MECs or a sorting mechanism