Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

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 den Berg, Jurjen J. Luykx, Orla Hardiman and Jan H. Veldink
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Russell L. McLaughlin: Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin
Dick Schijven: 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
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
Orla Hardiman: Smurfit Institute of Genetics, Trinity College Dublin
Jan H. Veldink: Brain Center Rudolf Magnus, University Medical Center Utrecht

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14774

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