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Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

Author

Listed:
  • Russell L. McLaughlin

    (Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin
    Smurfit Institute of Genetics, Trinity College Dublin)

  • Dick Schijven

    (Brain Center Rudolf Magnus, University Medical Center Utrecht
    Brain Center Rudolf Magnus, University Medical Center Utrecht)

  • Wouter van Rheenen

    (Brain Center Rudolf Magnus, University Medical Center Utrecht)

  • Kristel R. van Eijk

    (Brain Center Rudolf Magnus, University Medical Center Utrecht)

  • Margaret O’Brien

    (Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin)

  • René S. Kahn

    (Brain Center Rudolf Magnus, University Medical Center Utrecht)

  • Roel A. Ophoff

    (Brain Center Rudolf Magnus, University Medical Center Utrecht
    David Geffen School of Medicine, University of California
    Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California)

  • An Goris

    (Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven—University of Leuven)

  • Daniel G. Bradley

    (Smurfit Institute of Genetics, Trinity College Dublin)

  • Ammar Al-Chalabi

    (Maurice Wohl Clinical Neuroscience Institute, King’s College London)

  • Leonard H. van den Berg

    (Brain Center Rudolf Magnus, University Medical Center Utrecht)

  • Jurjen J. Luykx

    (Brain Center Rudolf Magnus, University Medical Center Utrecht
    Brain Center Rudolf Magnus, University Medical Center Utrecht
    Hospital Network Antwerp (ZNA) Stuivenberg and Sint Erasmus)

  • Orla Hardiman

    (Smurfit Institute of Genetics, Trinity College Dublin)

  • Jan H. Veldink

    (Brain Center Rudolf Magnus, University Medical Center Utrecht)

Abstract

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 × 10−4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 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.

Suggested Citation

  • Russell L. McLaughlin & Dick Schijven & Wouter van Rheenen & Kristel R. van Eijk & Margaret O’Brien & René S. Kahn & Roel A. Ophoff & An Goris & Daniel G. Bradley & Ammar Al-Chalabi & Leonard H. van d, 2017. "Genetic correlation between amyotrophic lateral sclerosis and schizophrenia," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14774
    DOI: 10.1038/ncomms14774
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