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Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data

  • 23 and Me Research Team
  • Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry and Behavioral Sciences & Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York.
  • Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University (LMU), Munich, Germany.
  • Departments of Neurology and Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia.
  • From the Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience (S.M.D.M., A.A., G.J.E.R.) and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht, Utrecht, The Netherlands; Division of Neurosurgery, Department of Critical Care, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong...
  • Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania.
  • Department of Medicine, University of Cambridge, Cambridge, CB2 OQQ, UK.
  • Genetics Institute, University College London, WC1E 6BT, London, United Kingdom.
  • Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
  • Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts.
  • BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, United Kingdom.
  • School of Social and Community Medicine, MRC Integrated Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom.
  • Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Endocrine Genetics Laboratory, Department of Pediatrics and the Child Health Program of the Research Institute, McGill University Health Centre, Montreal, Quebec, Canada.
  • Quantinuum Research LLC, San Diego, California.
  • Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Department of Dermatology, Veterans Affairs Hospital, University of Michigan, Ann Arbor, Michigan.
  • Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Division of Genetics and Molecular Medicine, King's College London, London, UK.
  • Department of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health School of Public Health, Imperial College London, London, United Kingdom.
  • K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway.

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)641-657
Number of pages17
JournalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics
Volume177
Issue number7
DOIs
Publication statusPublished - Oct 2018
Externally publishedYes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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