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

• DOI: 10.1038/s41467-020-17376-1
• Publication Date: 2020-08-11T10:05:13Z
• Authors: 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 Buitelaar; Erlend Bøen; Elisabeth Gulowse...; Simon Cervenka; Annette Conzelmann; David Coynel; Pasquale Di Carlo; Srdjan Djurovic; Sarah Eisenacher; Thomas Espeseth; Helena Fatouros-B...; Lena 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-Lin...; Torgeir Moberget; Jan Egil Nordvik; Lars Nyberg; Kevin S. O’ Connell; Jaap Oosterlaan; Marco Papalino; Andreas Papassoti...; Paul Pauli; Giulio Pergola; Karin Persson; Dominique de Quer...; 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
• Keywords: Genetic architecture; Pons

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 loci, including the first linked to midbrain, pons, medulla oblongata volumes, map them 305 genes. In replication 7432 participants most loci show same effect direction are significant at nominal threshold. We detect overlap between brainstem volumes eight psychiatric neurological disorders. additional clinical 5062 individuals with 11,257 healthy controls, observe differential volume alterations schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, Parkinson’s disease, supporting relevance