New Results
The genetic architecture of human brainstem structures and their involvement in common brain disorders
Torbjørn Elvsåshagen, Shahram Bahrami, Dennis van der Meer, Ingrid Agartz, Dag Alnæs, Deanna M. Barch, Ramona Baur-Streubel, Alessandro Bertolino, Mona K. Beyer, Giuseppe Blasi, Stefan Borgwardt, Birgitte Boye, Jan Buitelaar, Erlend Bøen, Elisabeth Gulowsen Celius, Simon Cervenka, Annette Conzelmann, David Coynel, Pasquale Di Carlo, Srdjan Djurovic, Sarah Eisenacher, Thomas Espeseth, Helena Fatouros-Bergman, Lena Flyckt, Barbara Franke, Oleksandr Frei, Barbara Gelao, Hanne Flinstad Harbo, Catharina A. Hartman, Asta Håberg, Dirk Heslenfeld, Pieter Hoekstra, Einar A. Høgestøl, Rune Jonassen, Erik G. Jönsson, Karolinska Schizophrenia Project (KaSP) consortium, Peter Kirsch, Iwona Kłoszewska, Trine Vik Lagerberg, Nils Inge Landrø, Stephanie Le Hellard, Klaus-Peter Lesch, Luigi A. Maglanoc, Ulrik F. Malt, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Torgeir Moberget, Jan Egil Nordvik, Lars Nyberg, Kevin S. O’Connell, Jaap Oosterlaan, Marco Papalino, Andreas Papassotiropoulos, Paul Pauli, Giulio Pergola, Karin Persson, Dominique de Quervain, Andreas Reif, Jarek Rokicki, Daan van Rooij, View ORCID ProfileAlexey A. Shadrin, André Schmidt, Emanuel Schwarz, Geir Selbæk, Hilkka Soininen, Piotr Sowa, Vidar M. Steen, Magda Tsolaki, Bruno Vellas, Lei Wang, Eric Westman, Georg Ziegler, Mathias Zink, Ole A. Andreassen, View ORCID ProfileLars T. Westlye, View ORCID ProfileTobias Kaufmann
doi: https://doi.org/10.1101/811711
Torbjørn Elvsåshagen
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
2Department of Neurology, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Shahram Bahrami
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Dennis van der Meer
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
4School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
Ingrid Agartz
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
5Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway
6Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Dag Alnæs
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Deanna M. Barch
7Departments of Psychological & Brain Sciences, Psychiatry, and Radiology, Washington University in St. Louis, St. Louis, USA
Ramona Baur-Streubel
8Department of Psychology I, University of Würzburg, Würzburg, Germany
Alessandro Bertolino
9Institute of Psychiatry, University of Bari, Bari, Italy
10Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy
Mona K. Beyer
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
11Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
Giuseppe Blasi
9Institute of Psychiatry, University of Bari, Bari, Italy
Stefan Borgwardt
12Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
13Institute of Psychiatry, King’s College, London, UK
14Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany
Birgitte Boye
15Psychosomatic and CL Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
16Department of Behavioural Sciences in Medicine, University of Oslo, Oslo, Norway
Jan Buitelaar
17Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
18Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands
Erlend Bøen
15Psychosomatic and CL Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Elisabeth Gulowsen Celius
2Department of Neurology, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Simon Cervenka
6Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Annette Conzelmann
19Children and Adolescence Psychiatry, University of Tübingen, Tübingen, Germany
David Coynel
20Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, CH-4055 Basel, Switzerland
21Division of Cognitive Neuroscience, Department of Psychology, University of Basel, Basel, Switzerland
Pasquale Di Carlo
10Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy
Srdjan Djurovic
22Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
23NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway
Sarah Eisenacher
24Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Thomas Espeseth
25Department of Psychology, University of Oslo, Oslo, Norway
Helena Fatouros-Bergman
6Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Lena Flyckt
6Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Barbara Franke
26Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
Oleksandr Frei
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Barbara Gelao
9Institute of Psychiatry, University of Bari, Bari, Italy
Hanne Flinstad Harbo
2Department of Neurology, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Catharina A. Hartman
27Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Asta Håberg
28Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway
29Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim, Norway
Dirk Heslenfeld
30Clinical Neuropsychology section, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
31Department of Cognitive Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Pieter Hoekstra
32Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Einar A. Høgestøl
2Department of Neurology, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Rune Jonassen
25Department of Psychology, University of Oslo, Oslo, Norway
33Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway
Erik G. Jönsson
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
6Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
34Members of Karolinska Schizophrenia Project (KaSP) consortium are listed at the end of the manuscript as collaborators
Peter Kirsch
35Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
36Bernstein Center for Computational Neuroscience Heidelberg/Mannheim, Mannheim, Germany
Iwona Kłoszewska
37Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland
Trine Vik Lagerberg
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Nils Inge Landrø
5Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway
25Department of Psychology, University of Oslo, Oslo, Norway
Stephanie Le Hellard
23NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway
Klaus-Peter Lesch
38Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany
39Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russia
40Dept. of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands
Luigi A. Maglanoc
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
25Department of Psychology, University of Oslo, Oslo, Norway
Ulrik F. Malt
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Patrizia Mecocci
41Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy
Ingrid Melle
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Andreas Meyer-Lindenberg
24Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Torgeir Moberget
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
25Department of Psychology, University of Oslo, Oslo, Norway
Jan Egil Nordvik
42The CatoSenteret Rehabilitation Center, Son, Norway
Lars Nyberg
43Departments of Radiation Sciences and Integrative Medical Biology, Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden
Kevin S. O’Connell
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Jaap Oosterlaan
30Clinical Neuropsychology section, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
44Emma Children’s Hospital Amsterdam UMC, University of Amsterdam, Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development, Amsterdam, The Netherlands
Marco Papalino
10Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy
Andreas Papassotiropoulos
20Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, CH-4055 Basel, Switzerland
21Division of Cognitive Neuroscience, Department of Psychology, University of Basel, Basel, Switzerland
45Psychiatric University Clinics, University of Basel, Basel, Switzerland
46Department Biozentrum, Life Sciences Training Facility, University of Basel, Basel, Switzerland
Paul Pauli
8Department of Psychology I, University of Würzburg, Würzburg, Germany
Giulio Pergola
10Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy
Karin Persson
47Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
48Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway
Dominique de Quervain
20Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, CH-4055 Basel, Switzerland
21Division of Cognitive Neuroscience, Department of Psychology, University of Basel, Basel, Switzerland
45Psychiatric University Clinics, University of Basel, Basel, Switzerland
Andreas Reif
49Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany
Jarek Rokicki
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Daan van Rooij
17Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
Alexey A. Shadrin
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
André Schmidt
12Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
Emanuel Schwarz
24Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Geir Selbæk
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
47Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
48Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway
Hilkka Soininen
50Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
51Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland
Piotr Sowa
11Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
Vidar M. Steen
23NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway
52Dr. E. Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway
Magda Tsolaki
53Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece
Bruno Vellas
54INSERM U 1027, University of Toulouse, Toulouse, France
Lei Wang
55Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
Eric Westman
13Institute of Psychiatry, King’s College, London, UK
56Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden
Georg Ziegler
38Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany
Mathias Zink
24Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
57District hospital Mittelfranken, Ansbach, Germany
Ole A. Andreassen
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Lars T. Westlye
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
25Department of Psychology, University of Oslo, Oslo, Norway
Tobias Kaufmann
1NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
ABSTRACT
Brainstem regions support critical bodily functions, yet their genetic architectures and involvement in brain disorders remain understudied. Here, we examined volumes of brainstem structures using magnetic resonance imaging in 43,353 individuals. In 27,034 genotyped healthy participants, we identified 16 genetic loci associated with whole brainstem volume and 10, 23, 3, and 9 loci associated with volumes of the midbrain, pons, superior cerebellar peduncle, and medulla oblongata, respectively. These loci were mapped to 305 genes, including genes linked to brainstem development and common brain disorders. We detected genetic overlap between the brainstem volumes and eight psychiatric and neurological disorders. Using imaging data from 16,319 additional individuals, we observed differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease. Together, our results provide new insights into the genetic underpinnings of brainstem structures and support their involvement in common brain disorders.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted October 21, 2019.
The genetic architecture of human brainstem structures and their involvement in common brain disorders
Torbjørn Elvsåshagen, Shahram Bahrami, Dennis van der Meer, Ingrid Agartz, Dag Alnæs, Deanna M. Barch, Ramona Baur-Streubel, Alessandro Bertolino, Mona K. Beyer, Giuseppe Blasi, Stefan Borgwardt, Birgitte Boye, Jan Buitelaar, Erlend Bøen, Elisabeth Gulowsen Celius, Simon Cervenka, Annette Conzelmann, David Coynel, Pasquale Di Carlo, Srdjan Djurovic, Sarah Eisenacher, Thomas Espeseth, Helena Fatouros-Bergman, Lena Flyckt, Barbara Franke, Oleksandr Frei, Barbara Gelao, Hanne Flinstad Harbo, Catharina A. Hartman, Asta Håberg, Dirk Heslenfeld, Pieter Hoekstra, Einar A. Høgestøl, Rune Jonassen, Erik G. Jönsson, Karolinska Schizophrenia Project (KaSP) consortium, Peter Kirsch, Iwona Kłoszewska, Trine Vik Lagerberg, Nils Inge Landrø, Stephanie Le Hellard, Klaus-Peter Lesch, Luigi A. Maglanoc, Ulrik F. Malt, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Torgeir Moberget, Jan Egil Nordvik, Lars Nyberg, Kevin S. O’Connell, Jaap Oosterlaan, Marco Papalino, Andreas Papassotiropoulos, Paul Pauli, Giulio Pergola, Karin Persson, Dominique de Quervain, Andreas Reif, Jarek Rokicki, Daan van Rooij, Alexey A. Shadrin, André Schmidt, Emanuel Schwarz, Geir Selbæk, Hilkka Soininen, Piotr Sowa, Vidar M. Steen, Magda Tsolaki, Bruno Vellas, Lei Wang, Eric Westman, Georg Ziegler, Mathias Zink, Ole A. Andreassen, Lars T. Westlye, Tobias Kaufmann
bioRxiv 811711; doi: https://doi.org/10.1101/811711
The genetic architecture of human brainstem structures and their involvement in common brain disorders
Torbjørn Elvsåshagen, Shahram Bahrami, Dennis van der Meer, Ingrid Agartz, Dag Alnæs, Deanna M. Barch, Ramona Baur-Streubel, Alessandro Bertolino, Mona K. Beyer, Giuseppe Blasi, Stefan Borgwardt, Birgitte Boye, Jan Buitelaar, Erlend Bøen, Elisabeth Gulowsen Celius, Simon Cervenka, Annette Conzelmann, David Coynel, Pasquale Di Carlo, Srdjan Djurovic, Sarah Eisenacher, Thomas Espeseth, Helena Fatouros-Bergman, Lena Flyckt, Barbara Franke, Oleksandr Frei, Barbara Gelao, Hanne Flinstad Harbo, Catharina A. Hartman, Asta Håberg, Dirk Heslenfeld, Pieter Hoekstra, Einar A. Høgestøl, Rune Jonassen, Erik G. Jönsson, Karolinska Schizophrenia Project (KaSP) consortium, Peter Kirsch, Iwona Kłoszewska, Trine Vik Lagerberg, Nils Inge Landrø, Stephanie Le Hellard, Klaus-Peter Lesch, Luigi A. Maglanoc, Ulrik F. Malt, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Torgeir Moberget, Jan Egil Nordvik, Lars Nyberg, Kevin S. O’Connell, Jaap Oosterlaan, Marco Papalino, Andreas Papassotiropoulos, Paul Pauli, Giulio Pergola, Karin Persson, Dominique de Quervain, Andreas Reif, Jarek Rokicki, Daan van Rooij, Alexey A. Shadrin, André Schmidt, Emanuel Schwarz, Geir Selbæk, Hilkka Soininen, Piotr Sowa, Vidar M. Steen, Magda Tsolaki, Bruno Vellas, Lei Wang, Eric Westman, Georg Ziegler, Mathias Zink, Ole A. Andreassen, Lars T. Westlye, Tobias Kaufmann
bioRxiv 811711; doi: https://doi.org/10.1101/811711
Subject Area
Subject Areas
- Biochemistry (5269)
- Bioengineering (3678)
- Bioinformatics (15796)
- Biophysics (7257)
- Cancer Biology (5629)
- Cell Biology (8099)
- Clinical Trials (138)
- Developmental Biology (4768)
- Ecology (7518)
- Epidemiology (2059)
- Evolutionary Biology (10578)
- Genetics (7733)
- Genomics (10137)
- Immunology (5194)
- Microbiology (13915)
- Molecular Biology (5387)
- Neuroscience (30785)
- Paleontology (215)
- Pathology (879)
- Pharmacology and Toxicology (1525)
- Physiology (2254)
- Plant Biology (5024)
- Synthetic Biology (1388)
- Systems Biology (4148)
- Zoology (812)