TY - JOUR
T1 - The genetic architecture of human brainstem structures and their involvement in common brain disorders
AU - Karolinska Schizophrenia Project (KaSP) consortium
AU - Elvsåshagen, Torbjørn
AU - Bahrami, Shahram
AU - van der Meer, Dennis
AU - Agartz, Ingrid
AU - Alnæs, Dag
AU - Barch, Deanna M.
AU - Baur-Streubel, Ramona
AU - Bertolino, Alessandro
AU - Beyer, Mona K.
AU - Blasi, Giuseppe
AU - Borgwardt, Stefan
AU - Boye, Birgitte
AU - Buitelaar, Jan
AU - Bøen, Erlend
AU - Celius, Elisabeth Gulowsen
AU - Cervenka, Simon
AU - Conzelmann, Annette
AU - Coynel, David
AU - Di Carlo, Pasquale
AU - Djurovic, Srdjan
AU - Eisenacher, Sarah
AU - Espeseth, Thomas
AU - Fatouros-Bergman, Helena
AU - Flyckt, Lena
AU - Franke, Barbara
AU - Frei, Oleksandr
AU - Gelao, Barbara
AU - Harbo, Hanne Flinstad
AU - Hartman, Catharina A.
AU - Håberg, Asta
AU - Heslenfeld, Dirk
AU - Hoekstra, Pieter J.
AU - Høgestøl, Einar A.
AU - Jonassen, Rune
AU - Jönsson, Erik G.
AU - Farde, L.
AU - Flyckt, L.
AU - Engberg, G.
AU - Erhardt S, S.
AU - Fatouros-Bergman, H.
AU - Cervenka, S.
AU - Schwieler, L.
AU - Piehl, F.
AU - Agartz, I.
AU - Collste, K.
AU - Victorsson, P.
AU - Malmqvist, A.
AU - Hedberg, M.
AU - Orhan, F.
AU - Wang, Lei
N1 - Funding Information:
Some authors received speaker’s honoraria from Lundbeck (T.E., G.B., and O.A.A.), Janssen Cilag (T.E.), Merck (E.H.), Sanofi Genzyme (E.H.), and Synovion (O.A.A). A.B. received speaker’s honoraria from Lundbeck, Otsuka, and Janssen Cilag and consultation fees from Biogen and Roche. J.B. has been a consultant to, member of advisory board of, and/or speaker for Shire, Roche, Medice, and Servier. E.G.C. has received personal fees from Almirall, Biogen, Merck, Roche and Teva, and grants and personal fees from Novartis and Sanofi. S.C. has received grant support from AstraZeneca as a coinvestigator and has served as a speaker for Otsuka. H.F.H. has received travel support, honoraria for advice or lecturing from Biogen Idec, Sanofi Genzyme, Merck, Novartis, Roche, and Teva and an unrestricted research grant from Novartis. N.I.L. has received consultation fees and travel support from Lundbeck. H.S. has received fees for advisory boards from ACImmune, Merck, and Novo Nordisk. P.S. has received honoraria for lecturing and travel support from Merck. M.T. has been member of advisory boards for Merck, IASIS Healthcare, ELPEN and FarmaSyn. M.Z. has received speaker fees for lectures, travel support and membership in advisory boards from Janssen Cilag, Lund-beck, Otsuka, Ferrer Pharma, Trommsdorff, Servier, and Roche. None of these external parties had any role in the analysis, writing or decision to publish this work. All other authors declare no competing interests.
Funding Information:
The author list between I.A. and M.Z. is in alphabetic order. The authors were funded by` the South-Eastern Norway Regional Health Authority 2015-078 (T.E.), 2013-123 (O.A.A.), 2014-097 (L.T.W.), 2015-073 (L.T.W.) and 2016-083 (L.T.W.), by the Research Council of Norway (276082 LifespanHealth (T.K.), 213837 (O.A.A), 223273 NORMENT (O.A.A.), 204966 (L.T.W.), 229129 (O.A.A.), 249795 (L.T.W.), 273345 (L.T.W.) and 283798 SYNSCHIZ (O.A.A.)), Stiftelsen Kristian Gerhard Jebsen, the European Research Council (ERCStG 802998 BRAINMINT (L.T.W.)), NVIDIA Corporation GPU Grant (T.K.), the Ebbe Frøland foundation, and a research grant from Mrs. Throne-Holst. The investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. This publication is solely the responsibility of the authors and does not necessarily represent the views of the National Institutes of Health investigators. Complete listings of participating sites and study investigators can be found at [http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf]. The AddNeuroMed consortium was led by Simon Lovestone, Bruno Vellas, Patrizia Mecocci, Magda Tsolaki, Iwona Kłoszewska, and Hilkka Soininen.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089359929&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089359929&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-17376-1
DO - 10.1038/s41467-020-17376-1
M3 - Article
C2 - 32782260
AN - SCOPUS:85089359929
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4016
ER -