Common genetic variants influence human subcortical brain structures.
Common genetic variants influence human subcortical brain structures.
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DOI：
10.1038/nature14101
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发表时间：
2015-04-09
期刊：
影响因子：
64.8
通讯作者：
Medland, Sarah E.
中科院分区：
文献类型：
--
作者：
Hibar, Derrek P.;Stein, Jason L.;Renteria, Miguel E.;Arias-Vasquez, Alejandro;Desrivieres, Sylvane;Jahanshad, Neda;Toro, Roberto;Wittfeld, Katharina;Abramovic, Lucija;Andersson, Micael;Aribisala, Benjamin S.;Armstrong, Nicola J.;Bernard, Manon;Bohlken, Marc M.;Boks, Marco P.;Bralten, Janita;Brown, Andrew A.;Chakravarty, M. Mallar;Chen, Qiang;Ching, Christopher R. K.;Cuellar-Partida, Gabriel;den Braber, Anouk;Giddaluru, Sudheer;Goldman, Aaron L.;Grimm, Oliver;Guadalupe, Tulio;Hass, Johanna;Woldehawariat, Girma;Holmes, Avram J.;Hoogman, Martine;Janowitz, Deborah;Jia, Tianye;Kim, Sungeun;Klein, Marieke;Kraemer, Bernd;Lee, Phil H.;Loohuis, Loes M. Olde;Luciano, Michelle;Macare, Christine;Mather, Karen A.;Mattheisen, Manuel;Milaneschi, Yuri;Nho, Kwangsik;Papmeyer, Martina;Ramasamy, Adaikalavan;Risacher, Shannon L.;Roiz-Santianez, Roberto;Rose, Emma J.;Salami, Alireza;Saemann, Philipp G.;Schmaal, Lianne;Schork, Andrew J.;Shin, Jean;Strike, Lachlan T.;Teumer, Alexander;van Donkelaar, Marjolein M. J.;van Eijk, Kristel R.;Walters, Raymond K.;Westlye, Lars T.;Whelan, Christopher D.;Winkler, Anderson M.;Zwiers, Marcel P.;Alhusaini, Saud;Athanasiu, Lavinia;Ehrlich, Stefan;Hakobjan, Marina M. H.;Hartberg, Cecilie B.;Haukvik, Unn K.;Heister, Angelien J. G. A. M.;Hoehn, David;Kasperaviciute, Dalia;Liewald, David C. M.;Lopez, Lorna M.;Makkinje, Remco R. R.;Matarin, Mar;Naber, Marlies A. M.;McKay, D. Reese;Needham, Margaret;Nugent, Allison C.;Puetz, Benno;Royle, Natalie A.;Shen, Li;Sprooten, Emma;Trabzuni, Daniah;van der Marel, Saskia S. L.;van Hulzen, Kimm J. E.;Walton, Esther;Wolf, Christiane;Almasy, Laura;Ames, David;Arepalli, Sampath;Assareh, Amelia A.;Bastin, Mark E.;Brodaty, Henry;Bulayeva, Kazima B.;Carless, Melanie A.;Cichon, Sven;Corvin, Aiden;Curran, Joanne E.;Czisch, Michael;de Zubicaray, Greig I.;Dillman, Allissa;Duggirala, Ravi;Dyer, Thomas D.;Erk, Susanne;Fedko, Iryna O.;Ferrucci, Luigi;Foroud, Tatiana M.;Fox, Peter T.;Fukunaga, Masaki;Gibbs, J. Raphael;Goering, Harald H. H.;Green, Robert C.;Guelfi, Sebastian;Hansell, Narelle K.;Hartman, Catharina A.;Hegenscheid, Katrin;Heinz, Andreas;Hernandez, Dena G.;Heslenfeld, Dirk J.;Hoekstra, Pieter J.;Holsboer, Florian;Homuth, Georg;Hottenga, Jouke-Jan;Ikeda, Masashi;Jack, Clifford R., Jr.;Jenkinson, Mark;Johnson, Robert;Kanai, Ryota;Keil, Maria;Kent, Jack W., Jr.;Kochunov, Peter;Kwok, John B.;Lawrie, Stephen M.;Liu, Xinmin;Longo, Dan L.;McMahon, Katie L.;Meisenzah, Eva;Melle, Ingrid;Mahnke, Sebastian;Montgomery, Grant W.;Mostert, Jeanette C.;Muehleisen, Thomas W.;Nalls, Michael A.;Nichols, Thomas E.;Nilsson, Lars G.;Noethen, Markus M.;Ohi, Kazutaka;Olvera, Rene L.;Perez-Iglesias, Rocio;Pike, G. Bruce;Potkin, Steven G.;Reinvang, Ivar;Reppermund, Simone;Rietschel, Marcella;Romanczuk-Seiferth, Nina;Rosen, Glenn D.;Rujescu, Dan;Schnell, Knut;Schofield, Peter R.;Smith, Colin;Steen, Vidar M.;Sussmann, Jessika E.;Thalamuthu, Anbupalam;Toga, Arthur W.;Traynor, Bryan J.;Troncoso, Juan;Turner, Jessica A.;Valdes Hernandez, Maria C.;van't Ent, Dennis;van der Brug, Marcel;van der Wee, Nic J. A.;van Tol, Marie-Jose;Veltman, Dick J.;Wassink, Thomas H.;Westman, Eric;Zielke, Ronald H.;Zonderman, Alan B.;Ashbrook, David G.;Hager, Reinmar;Lu, Lu;McMahon, Francis J.;Morris, Derek W.;Williams, Robert W.;Brunner, Han G.;Buckner, Randy L.;Buitelaar, Jan K.;Cahn, Wiepke;Calhoun, Vince D.;Cavalleri, Gianpiero L.;Crespo-Facorro, Benedicto;Dale, Anders M.;Davies, Gareth E.;Delanty, Norman;Depondt, Chantal;Djurovic, Srdjan;Drevets, Wayne C.;Espeseth, Thomas;Gollub, Randy L.;Ho, Beng-Choon;Hoffman, Wolfgang;Hosten, Norbert;Kahn, Rene S.;Le Hellard, Stephanie;Meyer-Lindenberg, Andreas;Mueller-Myhsok, Bertram;Nauck, Matthias;Nyberg, Lars;Pandolfo, Massimo;Penninx, Brenda W. J. H.;Roffman, Joshua L.;Sisodiya, Sanjay M.;Smoller, Jordan W.;van Bokhoven, Hans;van Haren, Neeltje E. M.;Voelzke, Henry;Walter, Henrik;Weiner, Michael W.;Wen, Wei;White, Tonya;Agartz, Ingrid;Andreassen, Ole A.;Blangero, John;Boomsma, Dorret I.;Brouwer, Rachel M.;Cannon, Dara M.;Cookson, Mark R.;de Geus, Eco J. C.;Deary, Ian J.;Donohoe, Gary;Fernandez, Guillen;Fisher, Simon E.;Francks, Clyde;Glahn, David C.;Grabe, Hans J.;Gruber, Oliver;Hardy, John;Hashimoto, Ryota;Pol, Hilleke E. Hulshoff;Joensson, Erik G.;Kloszewska, Iwona;Lovestone, Simon;Mattay, Venkata S.;Mecocci, Patrizia;McDonald, Colm;McIntosh, Andrew M.;Ophoff, Roel A.;Paus, Tomas;Pausova, Zdenka;Ryten, Mina;Sachdev, Perminder S.;Saykin, Andrew J.;Simmons, Andy;Singleton, Andrew;Soininen, Hilkka;Wardlaw, Joanna M.;Weale, Michael E.;Weinberger, Daniel R.;Adams, Hieab H. H.;Launer, Lenore J.;Seiler, Stephan;Schmidt, Reinhold;Chauhan, Ganesh;Satizabal, Claudia L.;Becker, James T.;Yanek, Lisa;van der Lee, Sven J.;Ebling, Maritza;Fischl, Bruce;Longstreth, W. T., Jr.;Greve, Douglas;Schmidt, Helena;Nyquist, Paul;Vinke, Louis N.;van Duijn, Cornelia M.;Xue, Luting;Mazoyer, Bernard;Bis, Joshua C.;Gudnason, Vilmundur;Seshadri, Sudha;Ikram, M. Arfan;Martin, Nicholas G.;Wright, Margaret J.;Schumann, Gunter;Franke, Barbara;Thompson, Paul M., Jr.;Medland, Sarah E.
人类大脑的高度复杂结构受到遗传影响的强烈影响。大脑皮层下区域与皮层区域形成回路，以协调运动、学习、记忆和动机，而回路的改变可能导致异常行为和疾病。为了研究常见的遗传变异如何影响这些大脑区域的结构，我们对来自50个队列的30，717名个体的7个皮质下区域的体积和来自磁共振图像的颅内体积进行了全基因组关联研究。我们确定了五个新的遗传变异影响壳核和尾状核的体积。我们还发现了更强有力的证据，三个位点与先前建立的影响海马体积和颅内体积。这些变体显示了对大脑结构的特定体积效应，而不是跨结构的全局效应。在壳核中发现了最强的效应，其中一个新的基因间位点对体积有可复制的影响（rs 945270; P = 1.08 × 10−33;解释的方差为0.52%），显示出改变脑和血液组织中KTN 1基因表达的证据。影响壳核体积的变异体聚集在调节细胞凋亡、轴突导向和囊泡运输的发育基因附近。这些遗传变异的鉴定提供了对人类大脑发育变异性原因的深入了解，并可能有助于确定神经精神功能障碍的机制。
The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
通过基础神经节电路的光遗传控制对帕金森运动行为的调节。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3
作者：
Boker S;Neale M;Maes H;Wilde M;Spiegel M;Brick T;Spies J;Estabrook R;Kenny S;Bates T;Mehta P;Fox J
通讯作者：
Fox J
影响因子：
25
作者：
Cohen, Michael X.;Schoene-Bake, Jan-Christoph;Weber, Bernd
通讯作者：
Weber, Bernd
影响因子：
30.8
作者：
Ikram, M. Arfan;Fornage, Myriam;Smith, Albert V.;Seshadri, Sudha;Schmidt, Reinhold;Debette, Stephanie;Vrooman, Henri A.;Sigurdsson, Sigurdur;Ropele, Stefan;Taal, H. Rob;Mook-Kanamori, Dennis O.;Coker, Laura H.;Longstreth, W. T., Jr.;Niessen, Wiro J.;DeStefano, Anita L.;Beiser, Alexa;Zijdenbos, Alex P.;Struchalin, Maksim;Jack, Clifford R., Jr.;Rivadeneira, Fernando;Uitterlinden, Andre G.;Knopman, David S.;Hartikainen, Anna-Liisa;Pennell, Craig E.;Thiering, Elisabeth;Steegers, Eric A. P.;Hakonarson, Hakon;Heinrich, Joachim;Palmer, Lyle J.;Jarvelin, Marjo-Riitta;McCarthy, Mark I.;Grant, Struan F. A.;St Pourcain, Beate;Timpson, Nicholas J.;Smith, George Davey;Sovio, Ulla;Nalls, Mike A.;Au, Rhoda;Hofman, Albert;Gudnason, Haukur;van der Lugt, Aad;Harris, Tamara B.;Meeks, William M.;Vernooij, Meike W.;van Buchem, Mark A.;Catellier, Diane;Jaddoe, Vincent W. V.;Gudnason, Vilmundur;Windham, B. Gwen;Wolf, Philip A.;van Duijn, Cornelia M.;Mosley, Thomas H., Jr.;Schmidt, Helena;Launer, Lenore J.;Breteler, Monique M. B.;DeCarli, Charles;Adair, Linda S.;Ang, Wei;Atalay, Mustafa;vanBeijsterveldt, Toos;Bergen, Nienke;Benke, Kelly;Berry, Diane;Coin, Lachlan;Davis, Oliver S. P.;Elliott, Paul;Flexeder, Claudia;Frayling, Tim;Gaillard, Romy;Groen-Blokhuis, Maria;Goh, Liang-Kee;Haworth, Claire M. A.;Hadley, Dexter;Hedebrand, Johannes;Hinney, Anke;Hirschhorn, Joel N.;Holloway, John W.;Holst, Claus;Hottenga, Jouke Jan;Horikoshi, Momoko;Huikari, Ville;Hypponen, Elina;Kilpelainen, Tuomas O.;Kirin, Mirna;Kowgier, Matthew;Lakka, Hanna-Maaria;Lange, Leslie A.;Lawlor, Debbie A.;Lehtimaki, Terho;Lewin, Alex;Lindgren, Cecilia;Lindi, Virpi;Maggi, Reedik;Marsh, Julie;Middeldorp, Christel;Millwood, Iona;Murray, Jeffrey C.;Nivard, Michel;Nohr, Ellen Aagaard;Ntalla, Ioanna;Oken, Emily;Panoutsopoulou, Kalliope;Pararajasingham, Jennifer;Rodriguez, Alina;Salem, Rany M.;Sebert, Sylvain;Siitonen, Niina;Strachan, David P.;Teo, Yik-Ying;Valcarcel, Beatriz;Willemsen, Gonneke;Zeggini, Eleftheria;Boomsma, Dorret I.;Cooper, Cyrus;Gillman, Matthew;Hocher, Berthold;Lakka, Timo A.;Mohlke, Karen L.;Dedoussis, George V.;Ong, Ken K.;Pearson, Ewan R.;Price, Thomas S.;Power, Chris;Raitakari, Olli T.;Saw, Seang-Mei;Scherag, Andre;Simell, Olli;Sorensen, Thorkild I. A.;Wilson, James F.
通讯作者：
Wilson, James F.