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

Rachel M BrouwerMarieke KleinKatrina L Grasby Hugo G Schnack Neda JahanshadJalmar TeeuwSophia I ThomopoulosEmma SprootenCarol E FranzNitin GogtayWilliam S KremenMatthew S PanizzonLoes M Olde LoohuisChristopher D WhelanMoji AghajaniClara AllozaDag Alnaes Eric ArtigesRosa Ayesa-ArriolaGareth J BarkerMark E BastinElisabet BlokErlend Bøen Isabella A BreukelaarJoanna K BrightElizabeth E L Buimer Robin Bülow Dara M CannonSimone CiufoliniNicolas A CrossleyChristienne G Damatac Paola DazzanCasper L de MolSonja M C de ZwarteSylvane Desrivieres Covadonga Martinez Diaz-CanejaNhat Trung DoanKatharina DohmJuliane Hilde Fröhner Janik GoltermannAntoine GrigisDominik GrotegerdLaura K M Han Mathew A HarrisCatharina A HartmanSarah J HeanyWalter HeindelDirk J HeslenfeldSarah HohmannBernd IttermannPhilip R JansenJoost JanssenTianye Jia Jiyang JiangChristiane JockwitzTemmuz KaraliDaniel Keeser Martijn G J C KoevoetsRhoshel K LenrootBerend MalchowRené C W MandlVicente MedelSusanne MeinertCatherine A Morgan Thomas W Mühleisen Leila NabulsiNils OpelVíctor Ortiz-García de la FozBronwyn J OversMarie-Laure Paillère MartinotRonny RedlichTiago Reis MarquesJonathan ReppleGloria RobertsGennady V Roshchupkin Nikita SetiamanElena ShumskayaFrederike SteinGustavo SudreShun TakahashiAnbupalam ThalamuthuDiana Tordesillas-GutiérrezAad van der LugtNeeltje E M van HarenJoanna Marguerite Wardlaw Wei WenHenk-Jan WestenengKatharina WittfeldAlyssa H ZhuAndre ZugmanNicola J ArmstrongGaia BonfiglioJanita BraltenShareefa Dalvie Gail DaviesMarta Di FortiLinda DingGary DonohoeAndreas J ForstnerJavier Gonzalez-PeñasJoao P O F T GuimaraesGeorg HomuthJouke- Jan Hottenga Maria J KnolJohn B J KwokStephanie Le Hellard Karen A Mather Yuri Milaneschi Derek W Morris Markus Maria Nöthen Sergi Papiol Marcella D C Rietschel Marcos Leite SantoroVidar M SteenJason L Stein Fabian StreitRick M TankardAlexander Teumer Dennis van 't Ent Dennis van der MeerKristel R van EijkEvangelos Vassos Javier Váquez-Bourgon Stephanie-H Wittnull nullHieab H H AdamsIngrid AgartzDavid AmesKatrin Amunts Ole Andreas Andreassen Celso Arango Tobias BanaschewskiBernhard T BauneSintia Nogueira Belangero Arun L W Bokde Dorret I BoomsmaRodrigo A BressanHenry Brodaty Jan K BuitelaarWiepke CahnSvenja CaspersSven CichonBenedicto Crespo-FacorroSimon R Cox Udo Dannlowski Torbjørn ElvsåshagenThomas EspesethPeter G FalkaiSimon E FisherHerta FlorJanice M Fullerton Hugh Garavan Penny A Gowland Hans Jörgen Grabe Tim Hahn Andreas Heinz Manon H J Hillegers Jacqueline HoarePieter J HoekstraMohammad Arfan Ikram Andrea Parolin JackowskiAndreas JansenErik G JönssonRene S KahnTilo KircherMayuresh S Korgaonkar Axel KrugHerve LemaitreUlrik F Malt Jean-Luc Martinot Colm McDonaldPhilip B MitchellRyan L Muetzel Robin M Murray Frauke NeesIgor NenadićJaap Oosterlaan Roel A OphoffPedro M PanBrenda W J H PenninxLuise PoustkaPerminder Singh SachdevGiovanni A SalumPeter R Schofield Gunter Schumann Philip Shaw Kang Sim Michael N Smolka Dan J Stein Julian N TrollorLeonard H van den BergJan Herman Veldink Henrik Walter Lars Tjelta WestlyeRobert WhelanTonya WhiteMargaret J Wright Sarah E Medland Barbara FrankePaul M ThompsonHilleke E Hulshoff Pol

Published in: Nature neuroscience (2022)

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.