The genetic architecture of human brainstem structures and their involvement in common brain disorders

Torbjørn Elvsåshagen (), Shahram Bahrami (), Dennis 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 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 J. Hoekstra, Einar A. Høgestøl, Rune Jonassen, Erik G. Jönsson, Peter Kirsch, Iwona Kłoszewska, Trine Vik Lagerberg, Nils Inge Landrø, Stephanie 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 Quervain, Andreas Reif, Jaroslav Rokicki, Daan 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 C. Ziegler, Mathias Zink, Ole A. Andreassen, Lars T. Westlye and Tobias Kaufmann ()
Additional contact information
Torbjørn Elvsåshagen: Oslo University Hospital
Shahram Bahrami: Oslo University Hospital
Dennis Meer: Oslo University Hospital
Ingrid Agartz: Diakonhjemmet Hospital
Dag Alnæs: Oslo University Hospital
Deanna M. Barch: Washington University in St. Louis
Ramona Baur-Streubel: University of Würzburg
Alessandro Bertolino: University of Bari
Mona K. Beyer: University of Oslo
Giuseppe Blasi: University of Bari
Stefan Borgwardt: University of Basel
Birgitte Boye: Oslo University Hospital
Jan Buitelaar: Radboud University Medical Center
Erlend Bøen: Oslo University Hospital
Elisabeth Gulowsen Celius: Oslo University Hospital
Simon Cervenka: Karolinska Institutet & Stockholm Health Care Services, Stockholm Region
Annette Conzelmann: University of Tübingen
David Coynel: University of Basel
Pasquale Carlo: University of Bari Aldo Moro
Srdjan Djurovic: Oslo University Hospital
Sarah Eisenacher: Heidelberg University
Thomas Espeseth: University of Oslo
Helena Fatouros-Bergman: Karolinska Institutet & Stockholm Health Care Services, Stockholm Region
Lena Flyckt: Karolinska Institutet & Stockholm Health Care Services, Stockholm Region
Barbara Franke: Radboud University Medical Center
Oleksandr Frei: Oslo University Hospital
Barbara Gelao: University of Bari
Hanne Flinstad Harbo: Oslo University Hospital
Catharina A. Hartman: University of Groningen, University Medical Center Groningen
Asta Håberg: Norwegian University of Science and Technology
Dirk Heslenfeld: Vrije Universiteit Amsterdam
Pieter J. Hoekstra: University Medical Center Groningen, University of Groningen
Einar A. Høgestøl: Oslo University Hospital
Rune Jonassen: University of Oslo
Erik G. Jönsson: Oslo University Hospital
Peter Kirsch: Heidelberg University
Iwona Kłoszewska: Medical University of Lodz
Trine Vik Lagerberg: Oslo University Hospital
Nils Inge Landrø: Diakonhjemmet Hospital
Stephanie Hellard: University of Bergen
Klaus-Peter Lesch: University of Würzburg
Luigi A. Maglanoc: Oslo University Hospital
Ulrik F. Malt: University of Oslo
Patrizia Mecocci: University of Perugia
Ingrid Melle: Oslo University Hospital
Andreas Meyer-Lindenberg: Heidelberg University
Torgeir Moberget: Oslo University Hospital
Jan Egil Nordvik: The CatoSenteret Rehabilitation Center
Lars Nyberg: Umeå University
Kevin S. O’ Connell: Oslo University Hospital
Jaap Oosterlaan: Vrije Universiteit Amsterdam
Marco Papalino: University of Bari Aldo Moro
Andreas Papassotiropoulos: University of Basel
Paul Pauli: University of Würzburg
Giulio Pergola: University of Bari Aldo Moro
Karin Persson: Oslo University Hospital
Dominique Quervain: University of Basel
Andreas Reif: University Hospital Frankfurt
Jaroslav Rokicki: Oslo University Hospital
Daan Rooij: Radboud University Medical Center
Alexey A. Shadrin: Oslo University Hospital
André Schmidt: University of Basel
Emanuel Schwarz: Heidelberg University
Geir Selbæk: University of Oslo
Hilkka Soininen: University of Eastern Finland
Piotr Sowa: Oslo University Hospital
Vidar M. Steen: University of Bergen
Magda Tsolaki: Aristotle University of Thessaloniki
Bruno Vellas: University of Toulouse
Lei Wang: Northwestern University
Eric Westman: Institute of Psychiatry, King’s College
Georg C. Ziegler: University of Würzburg
Mathias Zink: Heidelberg University
Ole A. Andreassen: Oslo University Hospital
Lars T. Westlye: Oslo University Hospital
Tobias Kaufmann: Oslo University Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.

Date: 2020
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DOI: 10.1038/s41467-020-17376-1

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