Technology Networks -- Genomic Research
Largest Study of Its Kind Finds Many Psychiatric Disorders Arise From the Same Genes (2019)
Original story from Massachusetts General Hospital
Largest Study of Its Kind Finds Many Psychiatric Disorders Arise From the Same Genes (2019)
Original story from Massachusetts General Hospital
Part 1: Genes, the Immune system & Psychiatric Disorders
Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data (2018) Affiliations 1Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry and Behavioral Sciences & Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York. 2Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University (LMU), Munich, Germany. 3Departments of Neurology and Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia. 4Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 5Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania. 6Department of Medicine, University of Cambridge, Cambridge, United Kingdom. 7Genetics Institute, University College London, WC1E 6BT, London, United Kingdom. 8Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany. 9Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts. 10BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, United Kingdom. 11School of Social and Community Medicine, MRC Integrated Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom. 12Center for Applied Genomics, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 13Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 14Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 15Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 16Endocrine Genetics Laboratory, Department of Pediatrics and the Child Health Program of the Research Institute, McGill University Health Centre, Montreal, Quebec, Canada. 17Quantinuum Research LLC, San Diego, California. 18Department of Dermatology, Veterans Affairs Hospital, University of Michigan, Ann Arbor, Michigan. 19Department of Biostatistics, University of Michigan, Ann Arbor, Michigan. 20Division of Genetics and Molecular Medicine, King's College London, London, UK. 21Department of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health School of Public Health, Imperial College London, London, United Kingdom. 22K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway. Abstract Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study. |
Affiliation
Abstract This paper discusses the current evidence from animal and human studies for a central role of inflammation in schizophrenia. In animal models, pre- or perinatal elicitation of the immune response may increase immune reactivity throughout life, and similar findings have been described in humans. Levels of pro-inflammatory markers, such as cytokines, have been found to be increased in the blood and cerebrospinal fluid of patients with schizophrenia. Numerous epidemiological and clinical studies have provided evidence that various infectious agents are risk factors for schizophrenia and other psychoses. For example, a large-scale epidemiological study performed in Denmark clearly showed that severe infections and autoimmune disorders are such risk factors. The vulnerability-stress-inflammation model may help to explain the role of inflammation in schizophrenia because stress can increase pro-inflammatory cytokines and may even contribute to a chronic pro-inflammatory state. Schizophrenia is characterized by risk genes that promote inflammation and by environmental stress factors and alterations of the immune system. Typical alterations of dopaminergic, serotonergic, noradrenergic, and glutamatergic neurotransmission described in schizophrenia have also been found in low-level neuroinflammation and consequently may be key factors in the generation of schizophrenia symptoms. Further support for the relevance of a low-level neuroinflammatory process in schizophrenia is provided by the loss of central nervous system volume and microglial activation demonstrated in neuroimaging studies. Last but not least, the benefit of anti-inflammatory medications found in some studies and the intrinsic anti-inflammatory and immunomodulatory effects of antipsychotics provide further support for the role of inflammation in this debilitating disease. 
The Relationship Between Neuroimmunity and Bipolar Disorder: Mechanism and Translational Application (2019) Affiliations 1Clinical Research Center, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. 2Clinical Research Center, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. 3Clinical Research Center, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. 4CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, 200031, China. 5Shanghai Key Laboratory of Psychotic Disorders, Shanghai, 201108, China. Abstract Neuroimmune system may be involved in the pathological process of bipolar disorder (BD), but the essential association is not fully understood. Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system (CNS). Meanwhile, neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized, such as neurotransmitter systems, neuroendocrine systems, neurotrophic factors, and oxidative stress. Simultaneously, related genes and immune changes in peripheral blood vary with it. Overall, neuroimmunity may play an important role in the pathogenesis of BD, and the inflammatory cytokines, especially interleukin-6 and tumor necrosis factor-alpha, have potential value for the clinical diagnosis and prognosis of BD, as well as predicting the therapeutic effects of drugs. Large-scale studies are needed to extend the evidence on neuroimmunity in BD, and to examine its clinical value for applications such as early prediction and treatment. |