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

Elvsåshagen, T.; Bahrami, S.; van der Meer, D.; Agartz, I.; Alnæs, D.; Barch, D. M. 7.; Baur-Streubel, R.; Bertolino, A.; Beyer, M. K.; Blasi, G.; Borgwardt, S.; Boye, B.; Buitelaar, J.; Bøen, E.; Gulowsen Celius, E.; Cervenka, S.; Conzelmann, A.; Coynel, D.; Di Carlo, P.; Djurovic, S.; Eisenacher, S.; Espeseth, T.; Fatouros-Bergman, H.; Flyckt, L.; Franke, B.; Frei, O.; Gelao, B.; Flinstad Harbo, H.; Hartman, C. A.; Håberg, A.; Heslenfeld, D.; Hoekstra, P.; Høgestøl, E. A.; Jonassen, R.; Jönsson, E. G.; Karolinska Schizophrenia Project (KaSP) consortium,; Kirsch, P.; Kłoszewska, I.; Lagerberg, T. V.; Nils Inge Landrø, N. I.; Le Hellard, S.; Lesch, K.; Maglanoc, L. A. Malt U. F.; Mecocci, P.; Melle, I.; Meyer-Lindenberg, A.; Moberget, T.; Nordvik, J. E.; Nyberg, L.; O`connell, K. S.; Oosterlaan, J.; Papalino, M.; Papassotiropoulos, A.; Pauli, P.; Pergola, G.; Persson, K.; de Quervain, D.; Reif, A.; Rokicki, J.; van Rooij, D.; Shadrin, A. A.; Schmidt, A.; Schwarz, E.; Selbæk, G.; Soininen, H.; Sowa, P.; Steen, V. M.; Tsolaki, M.; Vellas, B.; Wang, L.; Westman, E.; Ziegler, G.; Zink, M.; Andreassen, O. A.; Westlye, L. T.; Kaufmann, T.

doi:10.1038/s41467-020-17376-1

Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from 27,034 individuals, we identified brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and mapped them to 305 genes. We detected genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5,062 individuals with common brain disorders and 11,257 healthy controls, we observed 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.