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

Torbjørn Elvsåshagen*, Shahram Bahrami, Dennis van der Meer, I. 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, S. Cervenka, Annette Conzelmann, David Coynel, Pasquale Di Carlo, Srdjan DjurovicSarah Eisenacher, Thomas Espeseth, H. Fatouros-Bergman, L. 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, L. Farde, L. Flyckt, G. Engberg, S. Erhardt S, H. Fatouros-Bergman, S. Cervenka, L. Schwieler, F. Piehl, I. Agartz, K. Collste, P. Victorsson, A. Malmqvist, M. Hedberg, F. Orhan, C. M. Sellgren, 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, Jaroslav 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 C. Ziegler, Mathias Zink, Ole A. Andreassen, Lars T. Westlye, Tobias Kaufmann, Karolinska Schizophrenia Project (KaSP) consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number4016
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

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