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

Brouwer, R. M., Klein, M., Grasby, K. L., Schnack, H. G., Jahanshad, N., Teeuw, J., et al. (2022). Genetic variants associated with longitudinal changes in brain structure across the lifespan. Nature Neuroscience, 25, 421-432. doi:10.1038/s41593-022-01042-4.

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 Creators:
Brouwer, Rachel M.1, 2, Author
Klein, Marieke1, 3, 4, 5, Author
Grasby, Katrina L.6, Author
Schnack, Hugo G.1, 7, Author
Jahanshad, Neda8, Author
Teeuw, Jalmar1, Author
Thomopoulos, Sophia I.8, Author
Sprooten, Emma4, 5, Author
Franz, Carol E.3, Author
Gogtay, Nitin9, Author
Kremen, William S.3, 10, Author
Panizzon, Matthew S.3, Author
Olde Loohuis, Loes M. 11, Author
Whelan, Christopher D.12, Author
Aghajani, Moji13, 14, Author
Alloza, Clara15, Author
Alnæs, Dag16, 17, Author
Artiges, Eric18, Author
Ayesa-Arriola, Rosa19, 20, 21, Author
Barker, Gareth J.22, Author
Bastin, Mark E.23, AuthorBlok, Elisabet24, AuthorBøen, Erlend17, AuthorBreukelaar, Isabella A.25, AuthorBright, Joanna K.8, AuthorBuimer, Elizabeth E. L.1, AuthorBülow, Robin26, AuthorCannon, Dara M.27, AuthorCiufolini, Simone22, AuthorCrossley, Nicolas A.22, 28, AuthorDamatac, Christienne G.4, 5, AuthorDazzan, Paola22, AuthorDe Mol, Casper L.29, AuthorDe Zwarte, Sonja M. C.1, AuthorDesrivières, Sylvane22, AuthorDíaz-Caneja, Covadonga M.15, AuthorDoan, Nhat Trung16, AuthorDohm, Katharina30, AuthorFröhner, Juliane H.31, AuthorGoltermann, Janik30, AuthorGrigis, Antoine18, AuthorGrotegerd, Dominik30, AuthorHan, Laura K. M.13, AuthorHarris, Mathew A.23, AuthorHartman, Catharina A.32, AuthorHeany, Sarah J.33, AuthorHeindel, Walter34, AuthorHeslenfeld, Dirk J.2, AuthorHohmann, Sarah35, AuthorIttermann, Bernd36, AuthorJansen, Philip R.2, 13, 24, AuthorJanssen, Joost15, AuthorJia, Tianye22, 37, AuthorJiang, Jiyang38, AuthorJockwitz, Christiane39, 40, AuthorKarali, Temmuz41, AuthorKeeser, Daniel41, 42, AuthorKoevoets, Martijn G. J. C.1, AuthorLenroot, Rhoshel K.38, 43, 44, AuthorMalchow, Berend45, AuthorMandl, René C. W.1, AuthorMedel, Vicente28, AuthorMeinert, Susanne30, AuthorMorgan, Catherine A.46, 47, AuthorMühleisen, Thomas W.39, 40, 48, AuthorNabulsi, Leila27, AuthorOpel, Nils30, 49, AuthorOrtiz-García de la Foz, Víctor 19, 20, AuthorOvers, Bronwyn J.44, AuthorPaillère Martinot, Marie-Laure 18, AuthorRedlich, Ronny30, 50, AuthorMarques, Tiago Reis22, 51, AuthorRepple, Jonathan30, AuthorRoberts, Gloria38, AuthorRoshchupkin, Gennady V.29, AuthorSetiaman, Nikita1, 24, AuthorShumskaya, Elena4, 5, AuthorStein, Frederike52, AuthorSudre, Gustavo53, AuthorTakahashi, Shun41, 54, AuthorThalamuthu, Anbupalam38, AuthorTordesillas-Gutiérrez, Diana55, 56, AuthorVan der Lugt, Aad29, AuthorVan Haren, Neeltje E. M.1, 24, AuthorWardlaw, Joanna M.23, AuthorWen, Wei38, AuthorWesteneng, Henk-Jan1, AuthorWittfeld, Katharina26, 57, AuthorZhu, Alyssa H.8, AuthorZugman, Andre58, 59, AuthorArmstrong, Nicola J.60, AuthorBonfiglio, Gaia2, AuthorBralten, Janita4, 5, AuthorDalvie, Shareefa33, AuthorDavies, Gail23, AuthorDi Forti, Marta 22, AuthorDing, Linda8, AuthorDonohoe, Gary61, AuthorForstner, Andreas J.39, 52, 62, AuthorGonzalez-Peñas, Javier15, AuthorGuimaraes, Joao P. O. F. T.4, 5, AuthorHomuth, Georg26, AuthorHottenga, Jouke-Jan2, AuthorKnol, Maria J.29, AuthorKwok, John B. J.38, 63, AuthorLe Hellard, Stephanie64, 65, AuthorMather, Karen A.38, 44, AuthorMilaneschi, Yuri13, AuthorMorris, Derek W.61, AuthorNöthen, Markus M.62, AuthorPapiol, Sergi20, 41, AuthorRietschel, Marcella35, AuthorSantoro, Marcos L.58, 59, AuthorSteen, Vidar M.64, 65, AuthorStein, Jason L.66, AuthorStreit, Fabian35, AuthorTankard, Rick M.60, AuthorTeumer, Alexander26, AuthorVan 't Ent, Dennis 2, AuthorVan der Meer, Dennis16, 17, 67, AuthorVan Eijk, Kristel R.1, AuthorVassos, Evangelos22, 68, AuthorVázquez-Bourgon, Javier19, 20, 21, AuthorWitt, Stephanie H.35, Authorthe IMAGEN Consortium, Author              Adams, Hieab H. H.29, 69, AuthorAgartz, Ingrid16, 70, 71, AuthorAmes, David72, 73, AuthorAmunts, Katrin39, 40, AuthorAndreassen, Ole A.16, 17, AuthorArango, Celso15, AuthorBanaschewski, Tobias35, AuthorBaune, Bernhard T.30, 72, AuthorBelangero, Sintia I.58, 59, AuthorBokde, Arun L. W.74, AuthorBoomsma, Dorret I.2, AuthorBressan, Rodrigo A.58, 59, 75, AuthorBrodaty, Henry38, AuthorBuitelaar, Jan K.4, 5, 76, AuthorCahn, Wiepke1, 77, AuthorCaspers, Svenja39, 40, AuthorCichon, Sven39, 48, 78, AuthorCrespo Facorro, Benedicto 20, 79, AuthorCox, Simon R.23, 80, AuthorDannlowski, Udo30, AuthorElvsåshagen, Torbjørn16, 17, AuthorEspeseth, Thomas16, 81, AuthorFalkai, Peter G.41, AuthorFisher, Simon E.5, 82, Author           Flor, Herta35, AuthorFullerton, Janice M.38, 44, AuthorGaravan, Hugh83, AuthorGowland, Penny A.84, AuthorGrabe, Hans J.26, 57, AuthorHahn, Tim30, AuthorHeinz, Andreas85, AuthorHillegers, Manon1, 24, AuthorHoare, Jacqueline33, 86, AuthorHoekstra, Pieter J.32, AuthorIkram, Mohammad A.29, AuthorJackowski, Andrea P.58, 59, AuthorJansen, Andreas52, AuthorJönsson, Erik G.16, 70, AuthorKahn, Rene S.87, 88, AuthorKircher, Tilo52, AuthorKorgaonkar, Mayuresh S.25, AuthorKrug, Axel52, 89, AuthorLemaitre, Herve90, AuthorMalt, Ulrik F.16, AuthorMartinot, Jean-Luc18, AuthorMcDonald, Colm27, AuthorMitchell, Philip B.38, AuthorMuetzel, Ryan L.24, AuthorMurray, Robin M.27, AuthorNees, Frauke35, 91, AuthorNenadic, Igor52, AuthorOosterlaan, Jaap2, 92, AuthorOphoff, Roel A.11, 29, AuthorPan, Pedro M.58, 59, AuthorPenninx, Brenda W. J. H.13, AuthorPoustka, Luise45, AuthorSachdev, Perminder S.38, 93, AuthorSalum, Giovanni A.59, 94, 95, AuthorSchofield, Peter R.38, 44, AuthorSchumann, Gunter37, 85, AuthorShaw, Philip53, AuthorSim, Kang96, 97, AuthorSmolka, Michael N.31, AuthorStein, Dan J.33, AuthorTrollor, Julian38, AuthorVan den Berg, Leonard H.1, AuthorVeldink, Jan H.1, AuthorWalter, Henrik85, AuthorWestlye, Lars T.16, 17, AuthorWhelan, Robert74, AuthorWhite, Tonya24, 29, AuthorWright, Margaret J.98, AuthorMedland, Sarah E.6, AuthorFranke, Barbara4, 5, AuthorThompson, Paul M.8, AuthorHulshoff Pol, Hilleke E. 1, 7, Author more..
Affiliations:
1University Medical Center Utrecht , Utrecht, The Netherlands, ou_persistent22              
2VU Amsterdam, Amsterdam, The Netherlands, ou_persistent22              
3University of California, San Diego, La Jolla, CA, USA, ou_persistent22              
4Radboud University Medical Center, Nijmegen, The Netherlands, ou_persistent22              
5Donders Institute for Brain, Cognition and Behaviour, External Organizations, ou_55236              
6QIMR Berghofer Medical research institute, Brisbane, Australia, ou_persistent22              
7Utrecht University, Utrecht, The Netherlands, ou_persistent22              
8Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA, ou_persistent22              
9American Psychiatric Association, Washington, DC, USA, ou_persistent22              
10VA San Diego Center of Excellence for Stress and Mental Health , San Diego, CA, USA, ou_persistent22              
11University of California, Los Angeles, Los Angeles, CA, USA, ou_persistent22              
12Biogen Research and Development, Cambridge, MA, USA, ou_persistent22              
13Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands, ou_persistent22              
14Leiden University, Leiden, The Netherlands, ou_persistent22              
15CIBERSAM, School of Medicine, Madrid, Spain, ou_persistent22              
16University of Oslo, Oslo, Norway, ou_persistent22              
17Oslo University Hospital, Oslo, Norway, ou_persistent22              
18Université Paris Saclay, Gif-sur-Yvette, France, ou_persistent22              
19School of Medicine, University of Cantabria, Santander, Spain, ou_persistent22              
20CIBERSAM, Biomedical Research Network on Mental Health Area, Santander, Spain, ou_persistent22              
21Universidad de Cantabria, Santander, Spain, ou_persistent22              
22King’s College London, London, UK, ou_persistent22              
23University of Edinburgh, Edinburgh, UK, ou_persistent22              
24Sophia Children’s Hospital, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands, ou_persistent22              
25Westmead Institute for Medical Research, University of Sydney, Westmead, Australia, ou_persistent22              
26University Medicine Greifswald, Greifswald, Germany, ou_persistent22              
27College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland, ou_persistent22              
28School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile, ou_persistent22              
29Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands, ou_persistent22              
30University of Münster, Münster, Germany, ou_persistent22              
31Technische Universität Dresden, Dresden, Germany, ou_persistent22              
32University Medical Center Groningen, Groningen, The Netherlands, ou_persistent22              
33University of Cape Town, Cape Town, South Africa, ou_persistent22              
34University Hospital Münster, Münster, Germany, ou_persistent22              
35Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany, ou_persistent22              
36Physikalisch-Technische Bundesanstalt, Berlin, Germany, ou_persistent22              
37Fudan University , Shanghai, China, ou_persistent22              
38University of New South Wales, Sydney, Australia, ou_persistent22              
39Research Centre Jülich, Jülich, Germany, ou_persistent22              
40Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany, ou_persistent22              
41Ludwig Maximilian University Hospital, Munich, Germany, ou_persistent22              
42Munich Center for Neurosciences (MCN), Martinsried, Germany, ou_persistent22              
43School of Medicine, University of New Mexico, Albuquerque, NM, USA, ou_persistent22              
44Neuroscience Research Australia, Sydney, Australia, ou_persistent22              
45University Medical Center Göttingen, Göttingen, Germany, ou_persistent22              
46University of Auckland, Auckland, Auckland, New Zealand, ou_persistent22              
47Brain research New Zealand - Rangahau Roro Aotearoa, Auckland, New Zealand, ou_persistent22              
48University of Basel, Basel, Switzerland, ou_persistent22              
49Jena University Hospital/Friedrich-Schiller-University Jena, Jena, Germany, ou_persistent22              
50University of Halle, Halle, Germany, ou_persistent22              
51Imperial College London, London, UK, ou_persistent22              
52Philipps-University Marburg, Marburg, Germany, ou_persistent22              
53National Human Genome Research Institute, Bethesda, MD, USA, ou_persistent22              
54Wakayama Medical University, Wakayama, Japan, ou_persistent22              
55Marqués de Valdecilla University Hospital, Santander, Spain, ou_persistent22              
56Instituto de Física de Cantabria (UC-CSiC), Santander, Spain, ou_persistent22              
57German Center for Neurodegenerative Diseases (DZNE), Site rostock/Greifswald, Greifswald, Germany, ou_persistent22              
58Universidade Federal de São Paulo (UNiFESP) , São Paulo, Brazil, ou_persistent22              
59National institute of Developmental Psychiatry for Children and Adolescents (INPD), São Paulo, Brazil, ou_persistent22              
60Curtin University, Perth, Australia, ou_persistent22              
61National University of ireland Galway, Galway, Ireland, ou_persistent22              
62University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany, ou_persistent22              
63University of Sydney, Sydney, Australia, ou_persistent22              
64University of Bergen, Bergen, Norway, ou_persistent22              
65Haukeland University Hospital, Bergen, Norway, ou_persistent22              
66University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, ou_persistent22              
67Maastricht University, Maastricht, The Netherlands, ou_persistent22              
68NIHR Maudsley Biomedical research Centre, London, UK, ou_persistent22              
69Universidad Adolfo Ibanez , Santiago, Chile, ou_persistent22              
70Karolinska Institutet, Stockholm, Sweden, ou_persistent22              
71Diakonhjemmet Hospital, Oslo, Norway, ou_persistent22              
72University of Melbourne, Parkville, Australia, ou_persistent22              
73National Ageing Research Institute, Parkville, Australia, ou_persistent22              
74Trinity College Dublin, Dublin, Ireland, ou_persistent22              
75Instituto Ame Sua Mente , São Paulo, Brazil, ou_persistent22              
76Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands, ou_persistent22              
77Altrecht Mental Health institute, Utrecht, The Netherlands, ou_persistent22              
78University Hospital Basel, Basel, Switzerland, ou_persistent22              
79School of Medicine, University of Seville, Seville, Spain, ou_persistent22              
80Scottish imaging Network, Edinburgh, UK, ou_persistent22              
81Bjørknes College, Oslo, Norway, ou_persistent22              
82Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, ou_792549              
83University of Vermont , Burlington, VT, USA, ou_persistent22              
84University of Nottingham, Nottingham, UK, ou_persistent22              
85Charité Universitätsmedizin Berlin, Berlin, Germany, ou_persistent22              
86Peninsula Medical School, University of Plymouth, Plymouth, UK, ou_persistent22              
87Icahn School of Medicine at Mount Sinai, New York, NY, USA, ou_persistent22              
88James J. peters Department of Veterans Affairs Medical Center, Bronx, NY, USA, ou_persistent22              
89University of Bonn, Bonn, Germany, ou_persistent22              
90Université de Bordeaux, Bordeaux, France, ou_persistent22              
91University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany, ou_persistent22              
92Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands, ou_persistent22              
93Prince of Wales Hospital, Sydney, Australia, ou_persistent22              
94Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, ou_persistent22              
95Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, ou_persistent22              
96Institute of Mental Health, Singapore, Singapore, ou_persistent22              
97Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, ou_persistent22              
98University of Queensland, Brisbane, Australia, ou_persistent22              

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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.

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Language(s): eng - English
 Dates: 20222022
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41593-022-01042-4
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Title: Nature Neuroscience
  Other : Nat. Neurosci.
Source Genre: Journal
 Creator(s):
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Publ. Info: New York, NY : Nature America Inc.
Pages: - Volume / Issue: 25 Sequence Number: - Start / End Page: 421 - 432 Identifier: ISSN: 1097-6256
CoNE: https://pure.mpg.de/cone/journals/resource/954925610931