Age-dependent genetic variants associated with longitudinal changes in brain structure across the lifespan
Authors: Brouwer Rachel M. , Klein Marieke , Grasby Katrina L. , Schnack Hugo G. , Jahanshad Neda , Teeuw Jalmar , Thomopoulos Sophia I. , Sprooten Emma , Franz Carol E. , Gogtay Nitin , Kremen William S. , Panizzon Matthew S. , Olde Loohuis Loes M. , Whelan Christopher D. , Aghajani Moji , Alloza Clara , Alnæs Dag , Artiges Eric , Ayesa-Arriola Rosa , Barker Gareth J. , Bastin Mark E. , Blok Elisabet , Bøen Erlend , Breukelaar Isabella A. , Bright Joanna K. , Buimer Elizabeth E. L. , Bülow Robin , Cannon Dara M. , Ciufolini Simone , Crossley Nicolas A. , Damatac Christienne G. , Dazzan Paola , de Mol Casper L. , de Zwarte Sonja M. C. , Desrivières Sylvane , Díaz-Caneja Covadonga M. , Doan Nhat Trung , Dohm Katharina , Fröhner Juliane H. , Goltermann Janik , Grigis Antoine , Grotegerd Dominik , Han Laura K. M. , Harris Mathew A. , Hartman Catharina A. , Heany Sarah J. , Heindel Walter , Heslenfeld Dirk J. , Hohmann Sarah , Ittermann Bernd , Jansen Philip R. , Janssen Joost , Jia Tianye , Jiang Jiyang , Jockwitz Christiane , Karali Temmuz , Keeser Daniel , Koevoets Martijn G. J. C. , Lenroot Rhoshel K. , Malchow Berend , Mandl René C. W. , Medel Vicente , Meinert Susanne , Morgan Catherine A. , Mühleisen Thomas W. , Nabulsi Leila , Opel Nils , de la Foz Víctor Ortiz-García , Overs Bronwyn J. , Martinot Marie-Laure Paillère , Quinlan Erin B. , Redlich Ronny , Marques Tiago Reis , Repple Jonathan , Roberts Gloria , Roshchupkin Gennady V. , Setiaman Nikita , Shumskaya Elena , Stein Frederike , Sudre Gustavo , Takahashi Shun , Thalamuthu Anbupalam , Tordesillas-Gutiérrez Diana , van der Lugt Aad , van Haren Neeltje E. M. , Wardlaw Joanna M. , Wen Wei , Westeneng Henk-Jan , Wittfeld Katharina , Zhu Alyssa H. , Zugman Andre , Armstrong Nicola J. , Bonfiglio Gaia , Bralten Janita , Dalvie Shareefa , Davies Gail , Di Forti Marta , Ding Linda , Donohoe Gary , Forstner Andreas J. , Gonzalez-Peñas Javier , Guimaraes Joao P. O. F. T. , Homuth Georg , Hottenga Jouke-Jan , Knol Maria J. , Kwok John B. J. , Le Hellard Stephanie , Mather Karen A. , Milaneschi Yuri , Morris Derek W. , Nöthen Markus M. , Papiol Sergi , Rietschel Marcella , Santoro Marcos L. , Steen Vidar M. , Stein Jason L. , Streit Fabian , Tankard Rick M. , Teumer Alexander , van ‘t Ent Dennis , van der Meer Dennis , van Eijk Kristel R. , Vassos Evangelos , Vázquez-Bourgon Javier , Witt Stephanie H. ,   Alzheimer’s Disease Neuroimaging Initiative,   the IMAGEN consortium, Adams Hieab H. H. , Agartz Ingrid , Ames David , Amunts Katrin , Andreassen Ole A. , Arango Celso , Banaschewski Tobias , Baune Bernhard T. , Belangero Sintia I. , Bokde Arun L. W. , Boomsma Dorret I. , Bressan Rodrigo A. , Brodaty Henry , Buitelaar Jan K. , Cahn Wiepke , Caspers Svenja , Cichon Sven , Facorro Benedicto Crespo , Cox Simon R. , Dannlowski Udo , Elvsåshagen Torbjørn , Espeseth Thomas , Falkai Peter G. , Fisher Simon E. , Flor Herta , Fullerton Janice M. , Garavan Hugh , Gowland Penny A. , Grabe Hans J. , Hahn Tim , Heinz Andreas , Hillegers Manon , Hoare Jacqueline , Hoekstra Pieter J. , Ikram Mohammad A. , Jackowski Andrea P. , Jansen Andreas , Jönsson Erik G. , Kahn Rene S. , Kircher Tilo , Korgaonkar Mayuresh S. , Krug Axel , Lemaitre Herve , Malt Ulrik F. , Martinot Jean-Luc , McDonald Colm , Mitchell Philip B. , Muetzel Ryan L. , Murray Robin M. , Nees Frauke , Nenadic Igor , Oosterlaan Jaap , Ophoff Roel A. , Pan Pedro M. , Penninx Brenda W. J. H. , Poustka Luise , Sachdev Perminder S. , Salum Giovanni A. , Schofield Peter R. , Schumann Gunter , Shaw Philip , Sim Kang , Smolka Michael N. , Stein Dan J. , Trollor Julian , van den Berg Leonard H. , Veldink Jan H. , Walter Henrik , Westlye Lars T. , Whelan Robert , White Tonya , Wright Margaret J. , Medland Sarah E. , Franke Barbara , Thompson Paul M. , Hulshoff Pol Hilleke E. 
Published: April 2020

SummaryHuman brain structure changes throughout our lives. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental, and neurodegenerative diseases. Here, we identified common genetic variants that affect rates of brain growth or atrophy, in the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal MRI data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genesGPR139, DACH1andAPOEare 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 ageing.