The genetic architecture of human brainstem structures and their involvement in common brain disorders
Author:
Elvsåshagen Torbjørn, Bahrami Shahram, van der Meer Dennis, Agartz Ingrid, Alnæs Dag, Barch Deanna M., Baur-Streubel Ramona, Bertolino Alessandro, Beyer Mona K., Blasi Giuseppe, Borgwardt Stefan, Boye Birgitte, Buitelaar Jan, Bøen Erlend, Celius Elisabeth Gulowsen, Cervenka Simon, Conzelmann Annette, Coynel David, Carlo Pasquale Di, Djurovic Srdjan, Eisenacher Sarah, Espeseth Thomas, Fatouros-Bergman Helena, Flyckt Lena, Franke Barbara, Frei Oleksandr, Gelao Barbara, Harbo Hanne Flinstad, Hartman Catharina A., Håberg Asta, Heslenfeld Dirk, Hoekstra Pieter, Høgestøl Einar A., Jonassen Rune, Jönsson Erik G., Kirsch Peter, Kłoszewska Iwona, Lagerberg Trine Vik, Landrø Nils Inge, Hellard Stephanie Le, Lesch Klaus-Peter, Maglanoc Luigi A., Malt Ulrik F., Mecocci Patrizia, Melle Ingrid, Meyer-Lindenberg Andreas, Moberget Torgeir, Nordvik Jan Egil, Nyberg Lars, O’Connell Kevin S., Oosterlaan Jaap, Papalino Marco, Papassotiropoulos Andreas, Pauli Paul, Pergola Giulio, Persson Karin, de Quervain Dominique, Reif Andreas, Rokicki Jarek, van Rooij Daan, Shadrin Alexey A.ORCID, Schmidt André, Schwarz Emanuel, Selbæk Geir, Soininen Hilkka, Sowa Piotr, Steen Vidar M., Tsolaki Magda, Vellas Bruno, Wang Lei, Westman Eric, Ziegler Georg, Zink Mathias, Andreassen Ole A., Westlye Lars T.ORCID, Kaufmann TobiasORCID,
Abstract
ABSTRACTBrainstem 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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