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

被引：93

作者：

Brouwer, Rachel M. ^{[1
,2
]}

Klein, Marieke ^{[1
,3
,4
,5
]}

Grasby, Katrina L. ^{[6
]}

Schnack, Hugo G. ^{[1
,7
]}

Jahanshad, Neda ^{[8
]}

Teeuw, Jalmar ^{[1
]}

Thomopoulos, Sophia I. ^{[8
]}

Sprooten, Emma ^{[9
]}

Franz, Carol E. ^{[3
,10
]}

Gogtay, Nitin ^{[3
,11
]}

Kremen, William S. ^{[3
,10
,12
]}

Panizzon, Matthew S. ^{[3
,10
]}

Olde Loohuis, Loes M. ^{[13
]}

Whelan, Christopher D. ^{[14
]}

Aghajani, Moji ^{[15
,16
]}

Alloza, Clara ^{[17
]}

Alanaes, Dag ^{[18
,19
]}

Artiges, Eric ^{[20
]}

Ayesa-Arriola, Rosa ^{[21
,22
,23
]}

Barker, Gareth J. ^{[24
]}

Bastin, Mark E. ^{[25
,26
,27
]}

Blok, Elisabet ^{[28
]}

Boen, Erlend ^{[29
]}

Breukelaar, Isabella A. ^{[30
]}

Bright, Joanna K. ^{[8
]}

Buimer, Elizabeth E. L. ^{[1
]}

Bulow, Robin ^{[31
]}

Cannon, Dara M. ^{[31
]}

Ciufolini, Simone ^{[33
]}

Crossley, Nicolas A. ^{[33
,34
]}

Damatac, Christienne G. ^{[9
]}

Dazzan, Paola ^{[35
]}

de Mol, Casper L. ^{[36
]}

de Zwarte, Sonja M. C. ^{[1
]}

Desrivieres, Sylvane ^{[37
]}

Diaz-Caneja, Covadonga M. ^{[17
]}

Doan, Nhat Trung ^{[18
]}

Dohm, Katharina ^{[38
]}

Froehner, Juliane H. ^{[39
]}

Goltermann, Janik ^{[38
]}

Grigis, Antoine ^{[40
]}

Grotegerd, Dominik ^{[38
]}

Han, Laura K. M. ^{[15
]}

Harris, Mathew A. ^{[25
]}

Hartman, Catharina A. ^{[41
]}

Heany, Sarah J. ^{[42
]}

Heindel, Walter ^{[43
]}

Heslenfeld, Dirk J. ^{[44
]}

Hohmann, Sarah ^{[45
]}

Ittermann, Bernd ^{[46
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Brain Ctr, Dept Psychiat, Utrecht, Netherlands

[2] Vrije Univ Amsterdam, Ctr Neurogenom & Cognit Res, Amsterdam Neurosci, Dept Complex Trait Genet, Amsterdam, Netherlands

[3] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[4] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands

[5] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands

[6] QIMR Berghofer Med Res Inst, Psychiat Genet, Brisbane, Qld, Australia

[7] Univ Utrecht, Utrecht Inst Linguist OTS, Utrecht, Netherlands

[8] Univ Southern Calif, Keck Sch Med, Mark & Mary Stevens Neuroimaging & Informat Inst, Imaging Genet Ctr, Marina Del Rey, CA USA

[9] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Med Ctr, Nijmegen, Netherlands

[10] Univ Calif San Diego, Ctr Behav Genet Aging, La Jolla, CA 92093 USA

[11] Amer Psychiat Assoc, Washington, DC USA

[12] VA San Diego Ctr Excellence Stress & Mental Hlt, San Diego, CA USA

[13] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA

[14] Biogen Res & Dev, Cambridge, MA USA

[15] Vrije Univ, Amsterdam UMC, Amsterdam Publ Hlth & Amsterdam Neurosci, Dept Psychiat, Amsterdam, Netherlands

[16] Leiden Univ, Sect Forens Family & Youth Care, Inst Educ & Child Studies, Leiden, Netherlands

[17] Univ Complutense, Dept Child & Adolescent Psychiat, Inst Psychiat & Mental Hlth, Hosp Gen Univ Gregorio Maranon,Sch Med,IiSGM,CIBE, Madrid, Spain

[18] Univ Oslo, NORMENT Ctr, Oslo, Norway

[19] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[20] Univ Paris Saclay, Univ Paris Cite, INSERM U1299 Trajectoires Dev Psychiat,UMR 9010, Ecole Normale Super Paris Saclay,Ctr Borelli,CNRS, Gif Sur Yvette, France

[21] Univ Cantabria, Valdecilla Biomed Res Inst IDIVAL, Marques Valdecilla Univ Hosp HUMV, Sch Med, Santander, Spain

[22] CIBERSAM, Biomed Res Network Mental Hlth Area, Santander, Spain

[23] Univ Cantabria, Santander, Spain

[24] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Neuroimaging, London, England

[25] Univ Edinburgh, Dept Psychol, Lothian Birth Cohorts Grp, Edinburgh, Midlothian, Scotland

[26] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland

[27] Univ Edinburgh, Edinburgh Imaging, Edinburgh, Midlothian, Scotland

[28] Erasmus Univ, Dept Child & Adolescent Psychiat Psychol, Sophia Childrens Hosp, Med Ctr, Rotterdam, Netherlands

[29] Oslo Univ Hosp, Psychosomat & CL Psychiat, Oslo, Norway

[30] Univ Sydney, Westmead Inst Med Res, Brain Dynam Ctr, Westmead, NSW, Australia

[31] Univ Med Greifswald, Inst Diagnost Radiol & Neuroradiol, Greifswald, Germany

[32] Natl Univ Ireland Galway, Ctr Neuroimaging Cognit & Genom NICOG, Coll Med Nursing & Hlth Sci, Clin Neuroimaging Lab,NCBES Galway Neurosci Ctr, Galway, Ireland

[33] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychosis Studies, London, England

[34] Pontificia Univ Catolica Chile, Sch Med, Dept Psychiat, Santiago, Chile

[35] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, London, England

[36] Erasmus Univ, Med Ctr Rotterdam, Dept Neurol, Rotterdam, Netherlands

[37] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England

[38] Univ Munster, Inst Translat Psychiat, Munster, Germany

[39] Tech Univ Dresden, Dept Psychiat & Psychotherapy, Sect Syst Neurosci, Dresden, Germany

[40] Univ Paris Saclay, CEA, Neurospin, Gif Sur Yvette, France

[41] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands

[42] Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa

[43] Univ Hosp Munster, Clin Radiol, Munster, Germany

[44] Dept Expt & Clin Psychol, Amsterdam, Netherlands

[45] Heidelberg Univ, Med Fac Mannheim, Dept Child & Adolescent Psychiat & Psychotherapy, Cent Inst Mental Hlth, Mannheim, Germany

[46] Phys Tech Bundesanstalt, Berlin, Germany

[47] Amsterdam UMC, VUmc, Dept Human Genet, Amsterdam, Netherlands

[48] Fudan Univ, Ctr Populat Neurosci & Precis Med PONS, Inst Sci & Technol Brain Inspired Intelligence, Shanghai, Peoples R China

[49] Fudan Univ, MoE Key Lab Computat Neurosci & Brain Inspired In, Inst Sci & Technol Brain Inspired Intelligence, Shanghai, Peoples R China

[50] Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Precis Med PONS, SGDP Ctr, London, England

来源：

NATURE NEUROSCIENCE | 2022年 / 25卷 / 04期

关键词：

GENOME-WIDE ASSOCIATION; INDIVIDUAL-DIFFERENCES; SUSCEPTIBILITY LOCI; CORTICAL THICKNESS; SURFACE-AREA; EXPRESSION; METAANALYSIS; VOLUME; RISK; RELIABILITY;

D O I：

10.1038/s41593-022-01042-4

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes. 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.

引用

页码：421 / 432

页数：12

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