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 Djurovic; Sarah 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

doi:10.1038/s41467-020-17376-1

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 journal › Article › Academic › peer-review

18 Citations (Web of Science)

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 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 language	English
Article number	4016
Number of pages	14
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17376-1
Publication status	Published - 11 Aug 2020

Keywords

GENOME-WIDE ASSOCIATION
CHROMATIN-STATE DISCOVERY
PARKINSONS-DISEASE
SCHIZOPHRENIA
RISK
LOCI
SEGMENTATION
METAANALYSIS
SUSCEPTIBILITY
INDIVIDUALS

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10.1038/s41467-020-17376-1

Cite this

Elvsashagen, T., Bahrami, S., van der Meer, D., Agartz, I., Alnaes, D., Barch, D. M., Baur-Streubel, R., Bertolino, A., Beyer, M. K., Blasi, G., Borgwardt, S., Boye, B., Buitelaar, J., Boen, E., Celius, E. G., Cervenka, S., Conzelmann, A., Coynel, D., Di Carlo, P., ... Karolinska Schizophrenia Project Consortium (2020). The genetic architecture of human brainstem structures and their involvement in common brain disorders. Nature Communications, 11(1), [4016]. https://doi.org/10.1038/s41467-020-17376-1

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author = "Torbjorn Elvsashagen and Shahram Bahrami and {van der Meer}, Dennis and Ingrid Agartz and Dag Alnaes and Barch, {Deanna M.} and Ramona Baur-Streubel and Alessandro Bertolino and Beyer, {Mona K.} and Giuseppe Blasi and Stefan Borgwardt and Birgitte Boye and Jan Buitelaar and Erlend Boen and Celius, {Elisabeth Gulowsen} and Simon Cervenka and Annette Conzelmann and David Coynel and {Di Carlo}, Pasquale and Srdjan Djurovic and Sarah Eisenacher and Thomas Espeseth and Helena Fatouros-Bergman and Lena Flyckt and Barbara Franke and Oleksandr Frei and Barbara Gelao and Harbo, {Hanne Flinstad} and Hartman, {Catharina A.} and Asta Haberg and Dirk Heslenfeld and Hoekstra, {Pieter J.} and Hogestol, {Einar A.} and Rune Jonassen and Jonsson, {Erik G.} and Peter Kirsch and Iwona Kloszewska and Lagerberg, {Trine Vik} and Landro, {Nils Inge} and {Le Hellard}, Stephanie and Klaus-Peter Lesch and Maglanoc, {Luigi A.} and Malt, {Ulrik F.} and Patrizia Mecocci and Ingrid Melle and Andreas Meyer-Lindenberg and Torgeir Moberget and Nordvik, {Jan Egil} and Lars Nyberg and O'Connell, {Kevin S.} and {Karolinska Schizophrenia Project Consortium}",

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Elvsashagen, T, Bahrami, S, van der Meer, D, Agartz, I, Alnaes, D, Barch, DM, Baur-Streubel, R, Bertolino, A, Beyer, MK, Blasi, G, Borgwardt, S, Boye, B, Buitelaar, J, Boen, E, Celius, EG, 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, Harbo, HF, Hartman, CA, Haberg, A, Heslenfeld, D, Hoekstra, PJ, Hogestol, EA, Jonassen, R, Jonsson, EG, Kirsch, P, Kloszewska, I, Lagerberg, TV, Landro, NI, Le Hellard, S, Lesch, K-P, Maglanoc, LA, Malt, UF, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Moberget, T, Nordvik, JE, Nyberg, L, O'Connell, KS & Karolinska Schizophrenia Project Consortium 2020, 'The genetic architecture of human brainstem structures and their involvement in common brain disorders', Nature Communications, vol. 11, no. 1, 4016. https://doi.org/10.1038/s41467-020-17376-1

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T1 - The genetic architecture of human brainstem structures and their involvement in common brain disorders

AU - Elvsashagen, Torbjorn

AU - Bahrami, Shahram

AU - van der Meer, Dennis

AU - Agartz, Ingrid

AU - Alnaes, 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 - Boen, 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 - Haberg, Asta

AU - Heslenfeld, Dirk

AU - Hoekstra, Pieter J.

AU - Hogestol, Einar A.

AU - Jonassen, Rune

AU - Jonsson, Erik G.

AU - Kirsch, Peter

AU - Kloszewska, Iwona

AU - Lagerberg, Trine Vik

AU - Landro, Nils Inge

AU - Le Hellard, Stephanie

AU - Lesch, Klaus-Peter

AU - Maglanoc, Luigi A.

AU - Malt, Ulrik F.

AU - Mecocci, Patrizia

AU - Melle, Ingrid

AU - Meyer-Lindenberg, Andreas

AU - Moberget, Torgeir

AU - Nordvik, Jan Egil

AU - Nyberg, Lars

AU - O'Connell, Kevin S.

AU - Karolinska Schizophrenia Project Consortium

PY - 2020/8/11

Y1 - 2020/8/11

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. 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.

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. 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.

KW - GENOME-WIDE ASSOCIATION

KW - CHROMATIN-STATE DISCOVERY

KW - PARKINSONS-DISEASE

KW - SCHIZOPHRENIA

KW - RISK

KW - LOCI

KW - SEGMENTATION

KW - METAANALYSIS

KW - SUSCEPTIBILITY

KW - INDIVIDUALS

U2 - 10.1038/s41467-020-17376-1

DO - 10.1038/s41467-020-17376-1

M3 - Article

C2 - 32782260

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

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M1 - 4016

ER -