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

Author

Listed:
  • Torbjørn Elvsåshagen

    (Oslo University Hospital
    Oslo University Hospital
    University of Oslo)

  • Shahram Bahrami

    (Oslo University Hospital)

  • Dennis Meer

    (Oslo University Hospital
    Maastricht University)

  • Ingrid Agartz

    (Diakonhjemmet Hospital
    Karolinska Institutet & Stockholm Health Care Services, Stockholm Region
    Institute of Clinical Medicine, University of Oslo)

  • Dag Alnæs

    (Oslo University Hospital)

  • Deanna M. Barch

    (Washington University in St. Louis)

  • Ramona Baur-Streubel

    (University of Würzburg)

  • Alessandro Bertolino

    (University of Bari
    University of Bari Aldo Moro)

  • Mona K. Beyer

    (University of Oslo
    Oslo University Hospital)

  • Giuseppe Blasi

    (University of Bari
    University of Bari Aldo Moro)

  • Stefan Borgwardt

    (University of Basel
    Institute of Psychiatry, King’s College
    University of Lübeck)

  • Birgitte Boye

    (Oslo University Hospital
    University of Oslo)

  • Jan Buitelaar

    (Radboud University Medical Center
    Karakter Child and Adolescent Psychiatry University Centre)

  • Erlend Bøen

    (Oslo University Hospital)

  • Elisabeth Gulowsen Celius

    (Oslo University Hospital
    University of Oslo)

  • Simon Cervenka

    (Karolinska Institutet & Stockholm Health Care Services, Stockholm Region)

  • Annette Conzelmann

    (University of Tübingen)

  • David Coynel

    (University of Basel
    University of Basel)

  • Pasquale Carlo

    (University of Bari Aldo Moro)

  • Srdjan Djurovic

    (Oslo University Hospital
    University of Bergen)

  • Sarah Eisenacher

    (Heidelberg University
    Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University)

  • Thomas Espeseth

    (University of Oslo
    Bjørknes College, Lovisenberggata)

  • 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
    University of Oslo)

  • Catharina A. Hartman

    (University of Groningen, University Medical Center Groningen)

  • Asta Håberg

    (Norwegian University of Science and Technology
    St. Olavs Hospital)

  • Dirk Heslenfeld

    (Vrije Universiteit Amsterdam
    Vrije Universiteit Amsterdam)

  • Pieter J. Hoekstra

    (University Medical Center Groningen, University of Groningen)

  • Einar A. Høgestøl

    (Oslo University Hospital
    University of Oslo)

  • Rune Jonassen

    (University of Oslo
    Oslo Metropolitan University)

  • Erik G. Jönsson

    (Oslo University Hospital
    University of Oslo
    Karolinska Institutet & Stockholm Health Care Services, Stockholm Region)

  • Peter Kirsch

    (Heidelberg University
    Bernstein Center for Computational Neuroscience Heidelberg/Mannheim)

  • Iwona Kłoszewska

    (Medical University of Lodz)

  • Trine Vik Lagerberg

    (Oslo University Hospital)

  • Nils Inge Landrø

    (Diakonhjemmet Hospital
    University of Oslo)

  • Stephanie Hellard

    (University of Bergen)

  • Klaus-Peter Lesch

    (University of Würzburg
    Sechenov First Moscow State Medical University
    Maastricht University)

  • Luigi A. Maglanoc

    (Oslo University Hospital
    University of Oslo)

  • Ulrik F. Malt

    (University of Oslo)

  • Patrizia Mecocci

    (University of Perugia)

  • Ingrid Melle

    (Oslo University Hospital
    University of Oslo)

  • Andreas Meyer-Lindenberg

    (Heidelberg University)

  • Torgeir Moberget

    (Oslo University Hospital
    University of Oslo)

  • Jan Egil Nordvik

    (The CatoSenteret Rehabilitation Center)

  • Lars Nyberg

    (Umeå University)

  • Kevin S. O’ Connell

    (Oslo University Hospital)

  • Jaap Oosterlaan

    (Vrije Universiteit Amsterdam
    Emma Children’s Hospital Amsterdam UMC, University of Amsterdam, Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development)

  • Marco Papalino

    (University of Bari Aldo Moro)

  • Andreas Papassotiropoulos

    (University of Basel
    University of Basel
    University of Basel
    University of Basel)

  • Paul Pauli

    (University of Würzburg)

  • Giulio Pergola

    (University of Bari Aldo Moro)

  • Karin Persson

    (Oslo University Hospital
    Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust)

  • Dominique Quervain

    (University of Basel
    University of Basel
    University of Basel)

  • Andreas Reif

    (University Hospital Frankfurt)

  • Jaroslav Rokicki

    (Oslo University Hospital
    University of Oslo)

  • Daan Rooij

    (Radboud University Medical Center)

  • Alexey A. Shadrin

    (Oslo University Hospital
    University of Oslo)

  • André Schmidt

    (University of Basel)

  • Emanuel Schwarz

    (Heidelberg University)

  • Geir Selbæk

    (University of Oslo
    Oslo University Hospital
    Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust)

  • Hilkka Soininen

    (University of Eastern Finland
    Kuopio University Hospital)

  • Piotr Sowa

    (Oslo University Hospital)

  • Vidar M. Steen

    (University of Bergen
    Haukeland University Hospital)

  • Magda Tsolaki

    (Aristotle University of Thessaloniki)

  • Bruno Vellas

    (University of Toulouse)

  • Lei Wang

    (Northwestern University)

  • Eric Westman

    (Institute of Psychiatry, King’s College
    Care Sciences and Society, Karolinska Institute)

  • Georg C. Ziegler

    (University of Würzburg)

  • Mathias Zink

    (Heidelberg University
    District hospital Mittelfranken)

  • Ole A. Andreassen

    (Oslo University Hospital
    University of Oslo)

  • Lars T. Westlye

    (Oslo University Hospital
    University of Oslo)

  • Tobias Kaufmann

    (Oslo University Hospital
    University of Oslo)

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.

Suggested Citation

  • 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 & B, 2020. "The genetic architecture of human brainstem structures and their involvement in common brain disorders," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17376-1
    DOI: 10.1038/s41467-020-17376-1
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