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

Genetic variants associated with longitudinal changes in brain structure across the lifespan.
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DOI:
10.1038/s41593-022-01042-4
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发表时间:
2022-04
影响因子:
25
通讯作者:
Hulshoff Pol, Hilleke E.
Hulshoff Pol, Hilleke E.
中科院分区:
医学1区
文献类型:
--
作者:
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;Alanaes, Dag;Artiges, Eric;Ayesa-Arriola, Rosa;Barker, Gareth J.;Bastin, Mark E.;Blok, Elisabet;Boen, Erlend;Breukelaar, Isabella A.;Bright, Joanna K.;Buimer, Elizabeth E. L.;Bulow, Robin;Cannon, Dara M.;Ciufolini, Simone;Crossley, Nicolas A.;Damatac, Christienne G.;Dazzan, Paola;de Mol, Casper L.;de Zwarte, Sonja M. C.;Desrivieres, Sylvane;Diaz-Caneja, Covadonga M.;Doan, Nhat Trung;Dohm, Katharina;Froehner, 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, Rene C. W.;Medel, Vicente;Meinert, Susanne;Morgan, Catherine A.;Muehleisen, Thomas W.;Nabulsi, Leila;Opel, Nils;de la Foz, Victor Ortiz-Garcia;Overs, Bronwyn J.;Paillere Martinot, Marie-Laure;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-Gutierrez, 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-Penas, 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.;Noethen, 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;Vazquez-Bourgon, Javier;Witt, Stephanie H.;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;Crespo-Facorro, Benedicto;Cox, Simon R.;Dannlowski, Udo;Elvsashagen, Torbjorn;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;Jonsson, 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 N.;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.

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人的大脑结构在我们的一生中不断变化。改变的大脑生长或下降速度与广泛的精神病,发育和神经退行性疾病有关。在这里,我们确定了影响大脑生长或萎缩速率的常见遗传变异,这是对整个生命周期中大脑形态变化的第一个全基因组关联荟萃分析。来自15,640人的纵向MRI数据被用来计算15个大脑结构的变化率。最强有力地鉴定的基因GPR 139、DACH 1和APOE与代谢过程相关。我们证明了抑郁症、精神分裂症、认知功能、失眠、身高、体重指数和吸烟的全球遗传重叠。基因组研究结果暗示了大脑变化率中的早期大脑发育和神经退行性过程。识别参与大脑结构变化的变异可能有助于确定最佳和功能失调的大脑发育和衰老的生物学途径。
Human 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 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 ageing.
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