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.

Additional Metadata
Persistent URL dx.doi.org/10.1038/ncomms14774, hdl.handle.net/1765/98826
Journal Nature Communications
Note With cooperation of Project MinE GWAS Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium
Grant This work was funded by the European Commission 7th Framework Programme; grant id fp7/259867 - European multidisciplinary ALS network identification to cure motor neuron degeneration (EURO-MOTOR)
Citation
Mclaughlin, R.L, Schijven, D, van Rheenen, W, van Eijk, K.R, O'Brien, M, Kahn, R, … Veldink, J.H. (2017). Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nature Communications, 8. doi:10.1038/ncomms14774