Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

RL McLaughlin, D Schijven, W Van Rheenen, KR Van Eijk, M O'Brien, Project MinE GWAS Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, RS Kahn, RA Ophoff, A Goris, DG Bradley, A Al-Chalabi, LH Van Den Berg, JJ Luykx, O Hardiman, JH Veldink, Nilo Riva

Research output: Contribution to journalArticle

Abstract

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. © 2017 The Author(s).
Original languageEnglish
Article number14774
JournalNature Communications
Volume8
Issue number5
DOIs
Publication statusPublished - 2017

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schizophrenia
Amyotrophic Lateral Sclerosis
Schizophrenia
Genes
genome
loci
linkages
Genome-Wide Association Study
Linkage Disequilibrium
regression analysis
Comorbidity
disorders
Odds Ratio
estimates

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McLaughlin, RL., Schijven, D., Van Rheenen, W., Van Eijk, KR., O'Brien, M., Consortium, P. M. GWAS., ... Riva, N. (2017). Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nature Communications, 8(5), [14774]. https://doi.org/10.1038/ncomms14774

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. / McLaughlin, RL; Schijven, D; Van Rheenen, W; Van Eijk, KR; O'Brien, M; Consortium, Project MinE GWAS; Consortium, Schizophrenia Working Group of the Psychiatric Genomics; Kahn, RS; Ophoff, RA; Goris, A; Bradley, DG; Al-Chalabi, A; Van Den Berg, LH; Luykx, JJ; Hardiman, O; Veldink, JH; Riva, Nilo.

In: Nature Communications, Vol. 8, No. 5, 14774, 2017.

Research output: Contribution to journalArticle

McLaughlin, RL, Schijven, D, Van Rheenen, W, Van Eijk, KR, O'Brien, M, Consortium, PMGWAS, Consortium, SWGOTPG, Kahn, RS, Ophoff, RA, Goris, A, Bradley, DG, Al-Chalabi, A, Van Den Berg, LH, Luykx, JJ, Hardiman, O, Veldink, JH & Riva, N 2017, 'Genetic correlation between amyotrophic lateral sclerosis and schizophrenia', Nature Communications, vol. 8, no. 5, 14774. https://doi.org/10.1038/ncomms14774
McLaughlin RL, Schijven D, Van Rheenen W, Van Eijk KR, O'Brien M, Consortium PMGWAS et al. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nature Communications. 2017;8(5). 14774. https://doi.org/10.1038/ncomms14774
McLaughlin, RL ; Schijven, D ; Van Rheenen, W ; Van Eijk, KR ; O'Brien, M ; Consortium, Project MinE GWAS ; Consortium, Schizophrenia Working Group of the Psychiatric Genomics ; Kahn, RS ; Ophoff, RA ; Goris, A ; Bradley, DG ; Al-Chalabi, A ; Van Den Berg, LH ; Luykx, JJ ; Hardiman, O ; Veldink, JH ; Riva, Nilo. / Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. In: Nature Communications. 2017 ; Vol. 8, No. 5.
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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. © 2017 The Author(s).

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