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 K. Buitelaar, Erlend Bøen, Elisabeth Gulowsen Celius, Simon Červenka, 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 F. Harbo, Catharina A. Hartman, Asta K. Håberg, Dirk J. Heslenfeld, Pieter J. Hoekstra, Einar August Høgestøl, Rune Jonassen, Erik G. Jönsson, Lars Farde, Lena Flyckt, Göran Engberg, S. Erhardt S, Helena Fatouros‐Bergman, Simon Červenka, Lilly Schwieler, Fredrik Piehl, Ingrid Agartz, Karin Collste, Pauliina Victorsson, Anna Malmqvist, Magnus Hedberg, Funda Orhan, Carl M. Sellgren, Peter Kirsch, Iwona Kłoszewska, Trine Vik Lagerberg, Nils Inge Landrø, Stéphanie Le Hellard, Klaus‐Peter Lesch, Luigi A. Maglanoc, Ulrik Fredrik 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 J.‐F. de Quervain, Andreas Reif, Jaroslav Rokicki, Daan van Rooij, Alexey 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
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.