Genetic correlation between amyotrophic lateral sclerosis and schizophrenia.
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.
Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin DO2 DK07, Republic of Ireland.|Smurfit Institute of Genetics, Trinity College Dublin, Dublin D02 DK07, Republic of Ireland.
Russell L
RL
McLaughlin
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.|Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.
Dick
0000-0001-5190-7241
D
Schijven
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.
Wouter
W
van Rheenen
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.
Kristel R
KR
van Eijk
Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin DO2 DK07, Republic of Ireland.
Margaret
M
O'Brien
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.
René S
RS
Kahn
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.|Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.|Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California 90095, USA.
Roel A
RA
Ophoff
Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven-University of Leuven, Leuven B-3000, Belgium.
An
A
Goris
Smurfit Institute of Genetics, Trinity College Dublin, Dublin D02 DK07, Republic of Ireland.
Daniel G
DG
Bradley
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London WC2R 2LS, UK.
Ammar
0000-0002-4924-7712
A
Al-Chalabi
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.
Leonard H
LH
van den Berg
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.|Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.|Department of Psychiatry, Hospital Network Antwerp (ZNA) Stuivenberg and Sint Erasmus, Antwerp 2020, Belgium.
Jurjen J
JJ
Luykx
Smurfit Institute of Genetics, Trinity College Dublin, Dublin D02 DK07, Republic of Ireland.
Orla
O
Hardiman
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.
Jan H
JH
Veldink
D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D005190:Family; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D020412:Multifactorial Inheritance; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000235:genetics