289 results match your criteria: "Life and Brain Center[Affiliation]"

Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed.

View Article and Find Full Text PDF

We have tested published methods for capturing allelic heterogeneity and identifying loci of joint effects to uncover more of the "hidden heritability" of schizophrenia (SCZ). We used two tools, cojo-GCTA and multi-SNP, to analyze meta-statistics from the latest genome-wide association study (GWAS) on SCZ by the Psychiatric Genomics Consortium (PGC). Stepwise regression on markers with p values <10 in cojo-GCTA identified 96 independent signals.

View Article and Find Full Text PDF

Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders.

Transl Psychiatry

December 2017

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.

Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses.

View Article and Find Full Text PDF

Background And Objectives: There is considerable evidence that periconceptional maternal folate deficiency and coding variants in maternal genes coding for critical enzymes in the folate pathway are associated with neural tube defects (NTDs) in offspring. In a case-control study we investigated C677T polymorphism in the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene in case and control mothers of Pakistani origin, and compared these with the respective maternal folate concentrations measured at the time of delivery.

Methods And Study Design: A case-control study was conducted among 109 case and 100 control mothers identified through the Holy Family Hospital Rawalpindi, Quaid-i-Azam University, Islamabad, Pakistan.

View Article and Find Full Text PDF

Objective: Dystroglycan (DG) is an adhesion complex formed by two subunits, α-DG and β-DG. In skeletal muscle, DG is part of the dystrophin-glycoprotein complex that is crucial for sarcolemma stability and it is involved in a plethora of muscular dystrophy phenotypes. Due to the important role played by DG in skeletal muscle stability as well as in a wide variety of other tissues including brain and the peripheral nervous system, it is essential to investigate its genetic assembly and transcriptional regulation.

View Article and Find Full Text PDF

Background: Lymphedema (LE) is a chronic clinical manifestation of filarial nematode infections characterized by lymphatic dysfunction and subsequent accumulation of protein-rich fluid in the interstitial space-lymphatic filariasis. A number of studies have identified single nucleotide polymorphisms (SNPs) associated with primary and secondary LE. To assess SNPs associated with LE caused by lymphatic filariasis, a cross-sectional study of unrelated Ghanaian volunteers was designed to genotype SNPs in 285 LE patients as cases and 682 infected patients without pathology as controls.

View Article and Find Full Text PDF

Genome-Wide MicroRNA Analysis Implicates miR-30b/d in the Etiology of Alopecia Areata.

J Invest Dermatol

March 2018

Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. Electronic address:

Alopecia areata (AA) is one of the most common forms of human hair loss. Although genetic studies have implicated autoimmune processes in AA etiology, understanding of the etiopathogenesis is incomplete. Recent research has implicated microRNAs, a class of small noncoding RNAs, in diverse autoimmune diseases.

View Article and Find Full Text PDF

Psychiatric Genomics: An Update and an Agenda.

Am J Psychiatry

January 2018

From the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Departments of Genetics, Psychiatry, and Nutrition, University of North Carolina, Chapel Hill, N.C.; the Department of Psychiatry, Washington University School of Medicine, St Louis; the Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Oslo and Oslo University Hospital, Oslo; the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark; the Center for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark; the Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark; the Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry Centre, King's College London, London; the National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust, London; the Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland; the Institute of Human Genetics, University of Bonn, Bonn, Germany; the Department of Genomics, Life and Brain Center, Bonn, Germany; the Institute of Neuroscience and Medicine, Juelich, Germany; the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis; the Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and the Genetics Institute, University of Florida, Gainesville; the Department of Psychiatry, University of California-San Diego, La Jolla, Calif., the Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, and the Department of Psychiatry, Massachusetts General Hospital, Boston; the Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Mass.; and the MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, U.K.

The Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. This global effort is dedicated to rapid progress and open science, and in the past decade it has delivered an increasing flow of new knowledge about the fundamental basis of common psychiatric disorders. The PGC has recently commenced a program of research designed to deliver "actionable" findings-genomic results that 1) reveal fundamental biology, 2) inform clinical practice, and 3) deliver new therapeutic targets.

View Article and Find Full Text PDF

PDK4 Inhibits Cardiac Pyruvate Oxidation in Late Pregnancy.

Circ Res

December 2017

From the Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, MA (L.X.L., F.D.); Corrigan Minehan Heart Center, Massachusetts General Hospital, Boston (L.X.L., F.D., M.C.C., S.D., A.R.); Division of Cardiovascular Disease, University of Alabama at Birmingham (G.C.R.); Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia (S.Y., J.L., S.W., M.M., Z.A.); Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ (W.L., C.J., J.D.R.); and Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Germany (M.H., B.K.F.).

Rationale: Pregnancy profoundly alters maternal physiology. The heart hypertrophies during pregnancy, but its metabolic adaptations, are not well understood.

Objective: To determine the mechanisms underlying cardiac substrate use during pregnancy.

View Article and Find Full Text PDF

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS).

View Article and Find Full Text PDF

Obstructive lung diseases are common causes of disability and death worldwide. A hallmark feature is aberrant activation of G protein-dependent signaling cascades. Currently, drugs targeting single G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) are used to reduce airway tone.

View Article and Find Full Text PDF

A sudden aversive event produces escape behaviors, an innate response essential for survival in virtually all-animal species. Nuclei including the lateral habenula (LHb), the lateral hypothalamus (LH), and the midbrain are not only reciprocally connected, but also respond to negative events contributing to goal-directed behaviors. However, whether aversion encoding requires these neural circuits to ultimately prompt escape behaviors remains unclear.

View Article and Find Full Text PDF

Frequency-dependent drug screening using optogenetic stimulation of human iPSC-derived cardiomyocytes.

Sci Rep

August 2017

Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.

Side effects on cardiac ion channels are one major reason for new drugs to fail during preclinical evaluation. Herein we propose a simple optogenetic screening tool measuring extracellular field potentials (FP) from paced cardiomyocytes to identify drug effects over the whole physiological heart range, which is essential given the rate-dependency of ion channel function and drug action. Human induced pluripotent stem cell-derived cardiomyocytes were transduced with an adeno-associated virus to express Channelrhodopsin2 and plated on micro-electrode arrays.

View Article and Find Full Text PDF
Article Synopsis
  • There are significant differences in DNA methylation at specific sites in the human genome, but the full extent and purpose of these differences are still not well understood.
  • Researchers analyzed whole genome bisulfite sequencing data from monocytes of five donors, identifying 157 new differentially methylated regions (DMRs) that show varying relationships with chromatin states and histone marks but do not correlate with gene expression.
  • Further validation using genome-wide association studies on a larger group revealed that most DMRs are not captured by standard 450k methylation arrays, indicating these arrays miss a lot of methylation variation; genetic variations influence these methylation patterns, but their impact on gene expression is generally minimal.
View Article and Find Full Text PDF

Expert and self-assessment of lifetime symptoms and diagnosis of major depressive disorder in large-scale genetic studies in the general population: comparison of a clinical interview and a self-administered checklist.

Psychiatr Genet

October 2017

aDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim bInstitute of Human Genetics cDepartment of Genomics, Life and Brain Center, University of Bonn, Bonn dInstitute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University, Munich eDepartment of Psychiatry and Psychotherapy, University of Göttingen, Göttingen fInstitute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany gDepartment of Biomedicine, Division of Medical Genetics, University of Basel, Basel, Switzerland.

Major depression disorder (MDD) is a complex neuropsychiatric disorder and an increasing number of genetic risk variants are being identified. Investigation of their influence in the general population requires accurate and efficient assessment of depressive symptoms. Here, clinical interviews conducted by clinicians are the gold standard.

View Article and Find Full Text PDF

Diabetes-associated metabolites may aid the identification of new risk variants for type 2 diabetes. Using targeted metabolomics within a subsample of the German EPIC-Potsdam study (n = 2500), we tested previously published SNPs for their association with diabetes-associated metabolites and conducted an additional exploratory analysis using data from the exome chip including replication within 2,692 individuals from the German KORA F4 study. We identified a total of 16 loci associated with diabetes-related metabolite traits, including one novel association between rs499974 (MOGAT2) and a diacyl-phosphatidylcholine ratio (PC aa C40:5/PC aa C38:5).

View Article and Find Full Text PDF

Cardiomyocyte Regeneration: A Consensus Statement.

Circulation

August 2017

From Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg Eppendorf, Hamburg, Germany (T.E.); DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany (T.E.) and partner site Rhein/Main, Bad Nauheim, Germany (T.B.); Institute of Molecular Cardiology, University of Louisville, Louisville, KY (R.B.); Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (T.B.); Department of Internal Medicine II, University of Giessen, Germany (T.B.); German Center for Lung Research (DZHL), Giessen/Marburg Bad Nauheim, Bad Nauheim, Germany (T.B.); Krannert Institute of Cardiology and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (L.J.F.); Institute of Physiology I, Life and Brain Center, Medical Faculty, University of Bonn, Germany (B.K.F.); Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden (J.F.); International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy (M.G.); Donald Soffer Endowed Program in Regenerative Medicine, Miller School of Medicine, Miami, FL (J.M.H.); Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.M.H.); Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (S.H.); Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA (R.T.L.); Cedars-Sinai Heart Institute, Los Angeles, CA (E.M.); Cardiomyocyte Renewal Laboratory, Texas Heart Institute, Houston (J.F.M.); Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX (J.F.M.); Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH (J.D.M.); Departments of Pathology, Bioengineering, and Medicine/Cardiology, Institute for Stem Cell and Regenerative Medicine, and Center for Cardiovascular Biology, University of Washington, Seattle (C.E.M.); University of Oxford, Department of Physiology, Anatomy and Genetics, United Kingdom (P.R.R.) Regencor, Inc, Los Altos, CA (P.R.-L.); Departments of Internal Medicine (Division of Cardiology) and Molecular Biology, UT Southwestern Medical Center, Dallas, TX (H.A.S., J.A.H.); and Heart Institute, Integrated Regenerative Research Institute, and Biology Department, San Diego State University, CA (M.S.A.).

View Article and Find Full Text PDF

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

Transl Psychiatry

June 2017

Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide.

View Article and Find Full Text PDF

The fundamental role of the brain-specific myelin transcription factor 1-like (MYT1L) gene in cases of intellectual disability and in the etiology of neurodevelopmental disorders is increasingly recognized. Yet, its function remains under-investigated. Here, we identify a network of helix-loop-helix (HLH) transcriptional regulators controlled by MYT1L, as indicated by our analyses in human neural stem cells and in the human brain.

View Article and Find Full Text PDF

A hypoxic tumor microenvironment is linked to poor prognosis. It promotes tumor cell dedifferentiation and metastasis and desensitizes tumor cells to type-I IFN, chemotherapy, and irradiation. The cytoplasmic immunoreceptor retinoic acid-inducible gene-I (RIG-I) is ubiquitously expressed in tumor cells and upon activation by 5'-triphosphate RNA (3pRNA) drives the induction of type I IFN and immunogenic cell death.

View Article and Find Full Text PDF

Despite extensive efforts, half of patients with rare movement disorders such as hereditary spastic paraplegias and cerebellar ataxias remain genetically unexplained, implicating novel genes and unrecognized mutations in known genes. Non-coding DNA variants are suspected to account for a substantial part of undiscovered causes of rare diseases. Here we identified mutations located deep in introns of POLR3A to be a frequent cause of hereditary spastic paraplegia and cerebellar ataxia.

View Article and Find Full Text PDF

Facebook usage on smartphones and gray matter volume of the nucleus accumbens.

Behav Brain Res

June 2017

Department of Psychology, University of Bonn, Bonn, Germany; Center for Economics and Neuroscience, University of Bonn, Bonn, Germany.

A recent study has implicated the nucleus accumbens of the ventral striatum in explaining why online-users spend time on the social network platform Facebook. Here, higher activity of the nucleus accumbens was associated with gaining reputation on social media. In the present study, we touched a related research field.

View Article and Find Full Text PDF

Socioeconomic Status Interacts with the Genetic Effect of a Chromosome 9p21.3 Common Variant to Influence Coronary Artery Calcification and Incident Coronary Events in the Heinz Nixdorf Recall Study (Risk Factors, Evaluation of Coronary Calcium, and Lifestyle).

Circ Cardiovasc Genet

April 2017

From the Institute for Medical Informatics, Biometry and Epidemiology (B.S., S.F., M.F., L.E., S.P., R.E., S.M., K.-H.J.), West-German Heart and Vascular Center Essen, Department of Cardiology (A.A.M.), University of Duisburg-Essen, Germany; Institute for Medical Sociology, Centre for Health and Society, Medical Faculty, University Clinic Düsseldorf, Germany (N.D.); Institute of Human Genetics (A.J.F., M.M.N.), Department of Genomics, Life and Brain Center (A.J.F., M.M.N.), University of Bonn, Germany.

Background: Genetic variants of a locus within the chromosome 9p21.3 region are consistently associated with coronary artery disease and coronary artery calcification (CAC). The aim of this study was to examine whether a 9p21.

View Article and Find Full Text PDF

Dopaminergic neurotransmission in the mesocortical system is crucial for higher order cognition. Common variation on the dopamine D2 receptor (DRD2) gene has been linked to individual differences in dopaminergic signaling and was also repeatedly associated to cognitive markers. The relationship between dopaminergic genetic variants and neurostructural properties of the mesocortical system, however, has received little attention so far.

View Article and Find Full Text PDF

Genetic effects influencing risk for major depressive disorder in China and Europe.

Transl Psychiatry

March 2017

Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects.

View Article and Find Full Text PDF