Genetic variants associated with longitudinal changes in brain structure across the lifespan

Rachel M. Brouwer; Marieke Klein; the IMAGEN Consortium; Katrina L. Grasby; Hugo G. Schnack; Neda Jahanshad; Jalmar Teeuw; Sophia I. Thomopoulos; Emma Sprooten; Carol E. Franz; Nitin Gogtay; William S. Kremen; Matthew S. Panizzon; Loes M. Olde Loohuis; Christopher D. Whelan; Moji Aghajani; Clara Alloza; Dag Alnæs; Eric Artiges; Rosa Ayesa-Arriola; Gareth J. Barker; Mark E. Bastin; Elisabet Blok; Erlend Bøen; Isabella A. Breukelaar; Joanna K. Bright; Elizabeth E.L. Buimer; Robin Bülow; Dara M. Cannon; Simone Ciufolini; Nicolas A. Crossley; Christienne G. Damatac; Paola Dazzan; Casper L. de Mol; Sonja M.C. de Zwarte; Sylvane Desrivières; Philip R. Jansen; Joost Janssen; Gennady V. Roshchupkin; Nikita Setiaman; Aad van der Lugt; Neeltje E.M. van Haren; Jouke Jan Hottenga; Maria J. Knol; Alexander Teumer; Hieab H.H. Adams; Manon Hillegers; Mohammad A. Ikram; Ryan L. Muetzel; Roel A. Ophoff; Tonya White

doi:10.1038/s41593-022-01042-4

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Rachel M. Brouwer^*, Marieke Klein, the IMAGEN Consortium, Katrina L. Grasby, Hugo G. Schnack, Neda Jahanshad, Jalmar Teeuw, Sophia I. Thomopoulos, Emma Sprooten, Carol E. Franz, Nitin Gogtay, William S. Kremen, Matthew S. Panizzon, Loes M. Olde Loohuis, Christopher D. Whelan, Moji Aghajani, Clara Alloza, Dag Alnæs, Eric Artiges, Rosa Ayesa-ArriolaGareth J. Barker, Mark E. Bastin, Elisabet Blok, Erlend Bøen, Isabella A. Breukelaar, Joanna K. Bright, Elizabeth E.L. Buimer, Robin Bülow, Dara M. Cannon, Simone Ciufolini, Nicolas A. Crossley, Christienne G. Damatac, Paola Dazzan, Casper L. de Mol, Sonja M.C. de Zwarte, Sylvane Desrivières, Philip R. Jansen, Joost Janssen, Gennady V. Roshchupkin, Nikita Setiaman, Aad van der Lugt, Neeltje E.M. van Haren, Jouke Jan Hottenga, Maria J. Knol, Alexander Teumer, Hieab H.H. Adams, Manon Hillegers, Mohammad A. Ikram, Ryan L. Muetzel, Roel A. Ophoff, Tonya White

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

Original language	English
Pages (from-to)	421-432
Number of pages	12
Journal	Nature Neuroscience
Volume	25
Issue number	4
DOIs	https://doi.org/10.1038/s41593-022-01042-4
Publication status	Published - 5 Apr 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.

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10.1038/s41593-022-01042-4

https://hdl.handle.net/11370/11fc5d23-5c83-43ef-9c30-ada58a8d2d15Licence: Article 25fa Dutch Copyright Act

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Brouwer, R. M., Klein, M., the IMAGEN Consortium, Grasby, K. L., Schnack, H. G., Jahanshad, N., Teeuw, J., Thomopoulos, S. I., Sprooten, E., Franz, C. E., Gogtay, N., Kremen, W. S., Panizzon, M. S., Olde Loohuis, L. M., Whelan, C. D., Aghajani, M., Alloza, C., Alnæs, D., Artiges, E., ... White, T. (2022). Genetic variants associated with longitudinal changes in brain structure across the lifespan. Nature Neuroscience, 25(4), 421-432. https://doi.org/10.1038/s41593-022-01042-4

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abstract = "Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.",

author = "Brouwer, {Rachel M.} and Marieke Klein and {the IMAGEN Consortium} and Grasby, {Katrina L.} and Schnack, {Hugo G.} and Neda Jahanshad and Jalmar Teeuw and Thomopoulos, {Sophia I.} and Emma Sprooten and Franz, {Carol E.} and Nitin Gogtay and Kremen, {William S.} and Panizzon, {Matthew S.} and {Olde Loohuis}, {Loes M.} and Whelan, {Christopher D.} and Moji Aghajani and Clara Alloza and Dag Aln{\ae}s and Eric Artiges and Rosa Ayesa-Arriola and Barker, {Gareth J.} and Bastin, {Mark E.} and Elisabet Blok and Erlend B{\o}en and Breukelaar, {Isabella A.} and Bright, {Joanna K.} and Buimer, {Elizabeth E.L.} and Robin B{\"u}low and Cannon, {Dara M.} and Simone Ciufolini and Crossley, {Nicolas A.} and Damatac, {Christienne G.} and Paola Dazzan and {de Mol}, {Casper L.} and {de Zwarte}, {Sonja M.C.} and Sylvane Desrivi{\`e}res and Jansen, {Philip R.} and Joost Janssen and Roshchupkin, {Gennady V.} and Nikita Setiaman and {van der Lugt}, Aad and {van Haren}, {Neeltje E.M.} and Hottenga, {Jouke Jan} and Knol, {Maria J.} and Alexander Teumer and Adams, {Hieab H.H.} and Manon Hillegers and Ikram, {Mohammad A.} and Muetzel, {Ryan L.} and Ophoff, {Roel A.} and Tonya White",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2022",

month = apr,

day = "5",

doi = "10.1038/s41593-022-01042-4",

language = "English",

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Brouwer, RM, Klein, M, the IMAGEN Consortium, Grasby, KL, Schnack, HG, Jahanshad, N, Teeuw, J, Thomopoulos, SI, Sprooten, E, Franz, CE, Gogtay, N, Kremen, WS, Panizzon, MS, Olde Loohuis, LM, Whelan, CD, Aghajani, M, Alloza, C, Alnæs, D, Artiges, E, Ayesa-Arriola, R, Barker, GJ, Bastin, ME, Blok, E, Bøen, E, Breukelaar, IA, Bright, JK, Buimer, EEL, Bülow, R, Cannon, DM, Ciufolini, S, Crossley, NA, Damatac, CG, Dazzan, P, de Mol, CL, de Zwarte, SMC, Desrivières, S, Jansen, PR, Janssen, J , Roshchupkin, GV, Setiaman, N, van der Lugt, A , van Haren, NEM, Hottenga, JJ, Knol, MJ, Teumer, A, Adams, HHH, Hillegers, M , Ikram, MA , Muetzel, RL, Ophoff, RA & White, T 2022, 'Genetic variants associated with longitudinal changes in brain structure across the lifespan', Nature Neuroscience, vol. 25, no. 4, pp. 421-432. https://doi.org/10.1038/s41593-022-01042-4

TY - JOUR

T1 - Genetic variants associated with longitudinal changes in brain structure across the lifespan

AU - Brouwer, Rachel M.

AU - Klein, Marieke

AU - the IMAGEN Consortium

AU - Grasby, Katrina L.

AU - Schnack, Hugo G.

AU - Jahanshad, Neda

AU - Teeuw, Jalmar

AU - Thomopoulos, Sophia I.

AU - Sprooten, Emma

AU - Franz, Carol E.

AU - Gogtay, Nitin

AU - Kremen, William S.

AU - Panizzon, Matthew S.

AU - Olde Loohuis, Loes M.

AU - Whelan, Christopher D.

AU - Aghajani, Moji

AU - Alloza, Clara

AU - Alnæs, Dag

AU - Artiges, Eric

AU - Ayesa-Arriola, Rosa

AU - Barker, Gareth J.

AU - Bastin, Mark E.

AU - Blok, Elisabet

AU - Bøen, Erlend

AU - Breukelaar, Isabella A.

AU - Bright, Joanna K.

AU - Buimer, Elizabeth E.L.

AU - Bülow, Robin

AU - Cannon, Dara M.

AU - Ciufolini, Simone

AU - Crossley, Nicolas A.

AU - Damatac, Christienne G.

AU - Dazzan, Paola

AU - de Mol, Casper L.

AU - de Zwarte, Sonja M.C.

AU - Desrivières, Sylvane

AU - Jansen, Philip R.

AU - Janssen, Joost

AU - Roshchupkin, Gennady V.

AU - Setiaman, Nikita

AU - van der Lugt, Aad

AU - van Haren, Neeltje E.M.

AU - Hottenga, Jouke Jan

AU - Knol, Maria J.

AU - Teumer, Alexander

AU - Adams, Hieab H.H.

AU - Hillegers, Manon

AU - Ikram, Mohammad A.

AU - Muetzel, Ryan L.

AU - Ophoff, Roel A.

AU - White, Tonya

PY - 2022/4/5

Y1 - 2022/4/5

N2 - Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

AB - Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

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U2 - 10.1038/s41593-022-01042-4

DO - 10.1038/s41593-022-01042-4

M3 - Article

C2 - 35383335

AN - SCOPUS:85127652829

SN - 1097-6256

VL - 25

SP - 421

EP - 432

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 4

ER -

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Abstract

Bibliographical note

UN SDGs

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