TY - JOUR

T1 - Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

AU - McLaughlin, Russell L

AU - Schijven, Dick

AU - van Rheenen, Wouter

AU - van Eijk, Kristel R

AU - O'Brien, Margaret

AU - Kahn, René S

AU - Ophoff, Roel A

AU - Goris, An

AU - Bradley, Daniel G

AU - Al-Chalabi, Ammar

AU - van den Berg, Leonard H

AU - Luykx, Jurjen J

AU - Hardiman, Orla

AU - Veldink, Jan H

AU - Knight, Jo

AU - Project MinE GWAS Consortium

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

PY - 2017/3/21

Y1 - 2017/3/21

N2 - 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.

AB - 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.

KW - Amyotrophic lateral sclerosis

KW - Genetics research

KW - Motor neuron disease

KW - Schizophrenia

U2 - 10.1038/ncomms14774

DO - 10.1038/ncomms14774

M3 - Journal article

C2 - 28322246

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 14774

ER -