![]() A neuropsychiatric prodrome has been described in some people with ALS–FTD, and higher rates of schizophrenia and suicide have been reported in first and second degree relatives of those with ALS, particularly in kindreds associated with the C9orf72 hexanucleotide repeat expansion 2. Although ALS is often described as a primarily motor-system disease, extramotor involvement occurs in up to 50% of cases, with prominent executive and behavioural impairment, and behavioural variant frontotemporal dementia (FTD) in up to 14% of cases 1. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Īmyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative condition characterized by progressive loss of upper and lower motor neurons, leading to death from respiratory failure in 70% of patients within 3 years of symptom onset. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. 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. 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). Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. 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.
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