New Results
Analysis of Shared Heritability in Common Disorders of the Brain
V Anttila, B Bulik-Sullivan, H Finucane, R Walters, J Bras, L Duncan, V Escott-Price, G Falcone, P Gormley, R Malik, N Patsopoulos, S Ripke, Z Wei, D Yu, PH Lee, P Turley, IGAP consortium, IHGC consortium, ILAE Consortium on Complex Epilepsies, IMSGC consortium, IPDGC consortium, METASTROKE and Intracerebral Hemorrhage Studies of the International Stroke Genetics Consortium, Attention-Deficit Hyperactivity Disorder Working Group of the Psychiatric Genomics Consortium, Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium, Bipolar Disorders Working Group of the Psychiatric Genomics Consortium, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome and Obsessive Compulsive Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, G Breen, C Churchhouse, C Bulik, M Daly, M Dichgans, SV Faraone, R Guerreiro, P Holmans, K Kendler, B Koeleman, CA Mathews, AL Price, JM Scharf, P Sklar, J Williams, N Wood, C Cotsapas, A Palotie, JW Smoller, P Sullivan, J Rosand, A Corvin, BM Neale, on behalf of the Brainstorm consortium
doi: https://doi.org/10.1101/048991
V Anttila
*1
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
B Bulik-Sullivan
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
H Finucane
4 Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
5 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
R Walters
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
J Bras
6 Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
L Duncan
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
V Escott-Price
7 Cardiff University, Medical Research Council Center for Neuropsychiatric Genetics & Genomics, Institute of Psychology, Medicine & Clinical Neuroscience, Cardiff, Wales, 24 UK
G Falcone
8 Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
P Gormley
9 Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA
R Malik
10 Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
N Patsopoulos
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
11 Department of Neurology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA
S Ripke
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
12 Charite Universitatsmedizin Berlin, Berlin, Germany
Z Wei
13 Department of Computer Science, New Jersey Institute of Technology, New Jersey, USA
D Yu
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
9 Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA
PH Lee
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
9 Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA
P Turley
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
G Breen
14 Kings College London, Institute of Psychiatry, Psychology & Neuroscience, Social Genetics & Developmental Psychiatry Center, MRC, London, England
15 NIHR, Biomed Research Center for Mental Health, South London & Maudsley NHS Trust & Institute Psychiatry, London, England
C Churchhouse
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
C Bulik
16 Departments of Psychiatry and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
17 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
M Daly
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
M Dichgans
10 Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
18 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
SV Faraone
19 Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA
R Guerreiro
20 Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK
P Holmans
7 Cardiff University, Medical Research Council Center for Neuropsychiatric Genetics & Genomics, Institute of Psychology, Medicine & Clinical Neuroscience, Cardiff, Wales, 24 UK
K Kendler
21 Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
B Koeleman
22 Division Biomedical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands
CA Mathews
23 Department of Psychiatry and UF Genetics Institute, University of Florida: Gainesville, Florida, USA
AL Price
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
5 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
JM Scharf
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
8 Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
9 Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA
24 Division of Cognitive and Behavioral Neurology, Brigham and Women’s Hospital, Boston, MA, USA
25 Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
P Sklar
26 Icahn School of Medicine at Mount Sinai, New York, New York, USA
J Williams
7 Cardiff University, Medical Research Council Center for Neuropsychiatric Genetics & Genomics, Institute of Psychology, Medicine & Clinical Neuroscience, Cardiff, Wales, 24 UK
N Wood
20 Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK
27 Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, UK
28 Institute of Genetics, University College London, London, UK
C Cotsapas
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
29 Department of Neurology, Yale School of Medicine, New Haven, CT, USA
A Palotie
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
9 Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA
30 Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland
31 Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
JW Smoller
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
9 Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA
P Sullivan
16 Departments of Psychiatry and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
32 Department of Genetics and Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
J Rosand
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
8 Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
25 Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
A Corvin
† These authors jointly supervised this work
*2
33 Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Ireland
BM Neale
† These authors jointly supervised this work
*3
1 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
2 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
3 Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
Abstract
Disorders of the brain exhibit considerable epidemiological comorbidity and frequently share symptoms, provoking debate about the extent of their etiologic overlap. We quantified the genetic sharing of 25 brain disorders based on summary statistics from genome-wide association studies of 215,683 patients and 657,164 controls, and their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders show substantial sharing of common variant risk, while neurological disorders appear more distinct from one another. We observe limited evidence of sharing between neurological and psychiatric disorders, but do identify robust sharing between disorders and several cognitive measures, as well as disorders and personality types. We also performed extensive simulations to explore how power, diagnostic misclassification and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a source of risk for brain disorders and the value of heritability-based methods in understanding their etiology.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Posted September 06, 2017.
Analysis of Shared Heritability in Common Disorders of the Brain
V Anttila, B Bulik-Sullivan, H Finucane, R Walters, J Bras, L Duncan, V Escott-Price, G Falcone, P Gormley, R Malik, N Patsopoulos, S Ripke, Z Wei, D Yu, PH Lee, P Turley, IGAP consortium, IHGC consortium, ILAE Consortium on Complex Epilepsies, IMSGC consortium, IPDGC consortium, METASTROKE and Intracerebral Hemorrhage Studies of the International Stroke Genetics Consortium, Attention-Deficit Hyperactivity Disorder Working Group of the Psychiatric Genomics Consortium, Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium, Bipolar Disorders Working Group of the Psychiatric Genomics Consortium, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome and Obsessive Compulsive Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, G Breen, C Churchhouse, C Bulik, M Daly, M Dichgans, SV Faraone, R Guerreiro, P Holmans, K Kendler, B Koeleman, CA Mathews, AL Price, JM Scharf, P Sklar, J Williams, N Wood, C Cotsapas, A Palotie, JW Smoller, P Sullivan, J Rosand, A Corvin, BM Neale, on behalf of the Brainstorm consortium
bioRxiv 048991; doi: https://doi.org/10.1101/048991
Analysis of Shared Heritability in Common Disorders of the Brain
V Anttila, B Bulik-Sullivan, H Finucane, R Walters, J Bras, L Duncan, V Escott-Price, G Falcone, P Gormley, R Malik, N Patsopoulos, S Ripke, Z Wei, D Yu, PH Lee, P Turley, IGAP consortium, IHGC consortium, ILAE Consortium on Complex Epilepsies, IMSGC consortium, IPDGC consortium, METASTROKE and Intracerebral Hemorrhage Studies of the International Stroke Genetics Consortium, Attention-Deficit Hyperactivity Disorder Working Group of the Psychiatric Genomics Consortium, Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium, Bipolar Disorders Working Group of the Psychiatric Genomics Consortium, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome and Obsessive Compulsive Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, G Breen, C Churchhouse, C Bulik, M Daly, M Dichgans, SV Faraone, R Guerreiro, P Holmans, K Kendler, B Koeleman, CA Mathews, AL Price, JM Scharf, P Sklar, J Williams, N Wood, C Cotsapas, A Palotie, JW Smoller, P Sullivan, J Rosand, A Corvin, BM Neale, on behalf of the Brainstorm consortium
bioRxiv 048991; doi: https://doi.org/10.1101/048991
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