Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

McLaughlin, Russell L and Schijven, Dick and van Rheenen, Wouter and van Eijk, Kristel R and O'Brien, Margaret and Kahn, René S and Ophoff, Roel A and Goris, An and Bradley, Daniel G and Al-Chalabi, Ammar and van den Berg, Leonard H and Luykx, Jurjen J and Hardiman, Orla and Veldink, Jan H and Knight, Jo (2017) Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nature Communications, 8. ISSN 2041-1723

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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.

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Journal Article
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Nature Communications
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23 Nov 2017 00:29
Last Modified:
21 Sep 2020 02:30