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

Torbjorn Elvsashagen*, Shahram Bahrami*, Dennis van der Meer, Ingrid Agartz, Dag Alnaes, Deanna M. Barch, Ramona Baur-Streubel, Alessandro Bertolino, Mona K. Beyer, Giuseppe Blasi, Stefan Borgwardt, Birgitte Boye, Jan Buitelaar, Erlend Boen, Elisabeth Gulowsen Celius, Simon Cervenka, Annette Conzelmann, David Coynel, Pasquale Di Carlo, Srdjan DjurovicSarah Eisenacher, Thomas Espeseth, Helena Fatouros-Bergman, Lena Flyckt, Barbara Franke, Oleksandr Frei, Barbara Gelao, Hanne Flinstad Harbo, Catharina A. Hartman, Asta Haberg, Dirk Heslenfeld, Pieter J. Hoekstra, Einar A. Hogestol, Rune Jonassen, Erik G. Jonsson, Peter Kirsch, Iwona Kloszewska, Trine Vik Lagerberg, Nils Inge Landro, 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, Karolinska Schizophrenia Project Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.

Original languageEnglish
Article number4016
Number of pages14
JournalNature Communications
Issue number1
Publication statusPublished - 11 Aug 2020


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