Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

• Published in: Nature communications Vol. 8; no. 1; p. 14774
• Main Authors: McLaughlin, Russell L., Schijven, Dick, van Rheenen, Wouter, van Eijk, Kristel R., O’Brien, Margaret, Kahn, René S., Ophoff, Roel A., Goris, An, Bradley, Daniel G., Al-Chalabi, Ammar, van den Berg, Leonard H., Luykx, Jurjen J., Hardiman, Orla, Veldink, Jan H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.03.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/378/1689/1285; 631/378/1689/1799; 692/308/2056; 692/617/375/1917; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - epidemiology; Amyotrophic Lateral Sclerosis - genetics; Case-Control Studies; Cohort Studies; Comorbidity; Consortia; Disease; Estimates; Family; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomes; Genomics; Human health and pathology; Humanities and Social Sciences; Humans; Life Sciences; Linear Models; Linkage Disequilibrium; Medicin och hälsovetenskap; multidisciplinary; Multifactorial Inheritance; Neurology; Neurosciences; Odds Ratio; Polymorphism, Single Nucleotide; Schizophrenia; Schizophrenia - epidemiology; Schizophrenia - genetics; Science; Science (multidisciplinary); White People - genetics; Working groups; Los Angeles California; Netherlands; California; Belgium; United States > US; Ireland
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14774

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. Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.