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  Genetic architecture of subcortical brain structures in 38,851 individuals

Satizabal, C. L., Adams, H. H. H., Hibar, D. P., White, C. C., Knol, M. J., Stein, J. L., et al. (2019). Genetic architecture of subcortical brain structures in 38,851 individuals. NATURE GENETICS, 51(11), 1624-1636. doi:10.1038/s41588-019-0511-y.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0009-6567-2 Version Permalink: https://hdl.handle.net/21.11116/0000-0009-6568-1
Genre: Journal Article

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Satizabal, Claudia L., Author
Adams, Hieab H. H., Author
Hibar, Derrek P., Author
White, Charles C., Author
Knol, Maria J., Author
Stein, Jason L., Author
Scholz, Markus, Author
Sargurupremraj, Muralidharan, Author
Jahanshad, Neda, Author
Roshchupkin V, Gennady, Author
Smith V, Albert, Author
Bis, Joshua C., Author
Jian, Xueqiu, Author
Luciano, Michelle, Author
Hofer, Edith, Author
Teumer, Alexander, Author
van der Lee, Sven J., Author
Yang, Jingyun, Author
Yanek, Lisa R., Author
Lee V, Tom, Author
Li, Shuo, AuthorHu, Yanhui, AuthorKoh, Jia Yu, AuthorEicher, John D., AuthorDesrivieres, Sylvane, AuthorArias-Vasquez, Alejandro, AuthorChauhan, Ganesh, AuthorAthanasiu, Lavinia, AuthorRentera, Miguel E., AuthorKim, Sungeun, AuthorHoehn, David1, Author           Armstrong, Nicola J., AuthorChen, Qiang, AuthorHolmes, Avram J., Authorden Braber, Anouk, AuthorKloszewska, Iwona, AuthorAndersson, Micael, AuthorEspeseth, Thomas, AuthorGrimm, Oliver, AuthorAbramovic, Lucija, AuthorAlhusaini, Saud, AuthorMilaneschi, Yuri, AuthorPapmeyer, Martina, AuthorAxelsson, Tomas, AuthorEhrlich, Stefan, AuthorRoiz-Santianez, Roberto, AuthorKraemer, Bernd, AuthorHaberg, Asta K., AuthorJones, Hannah J., AuthorPike, G. Bruce, AuthorStein, Dan J., AuthorStevens, Allison, AuthorBralten, Janita, AuthorVernooij, Meike W., AuthorHarris, Tamara B., AuthorFilippi, Irina, AuthorWitte, A. Veronica, AuthorGuadalupe, Tulio, AuthorWittfeld, Katharina, AuthorMosley, Thomas H., AuthorBecker, James T., AuthorNhat Doan, Trung, AuthorHagenaars, Saskia P., AuthorSaba, Yasaman, AuthorCuellar-Partida, Gabriel, AuthorAmin, Najaf, AuthorHilal, Saima, AuthorNho, Kwangsik, AuthorMirza-Schreiber, Nazanin2, Author           Arfanakis, Konstantinos, AuthorBecker, Diane M., AuthorAmes, David, AuthorGoldman, Aaron L., AuthorLee, Phil H., AuthorBoomsma I, Dorret, AuthorLovestone, Simon, AuthorGiddaluru, Sudheer, AuthorLe Hellard, Stephanie, AuthorMattheisen, Manuel, AuthorBohlken, Marc M., AuthorKasperaviciute, Dalia, AuthorSchmaal, Lianne, AuthorLawrie, Stephen M., AuthorAgartz, Ingrid, AuthorWalton, Esther, AuthorTordesillas-Gutierrez, Diana, AuthorDavies, Gareth E., AuthorShin, Jean, AuthorIpser, Jonathan C., AuthorVinke, Louis N., AuthorHoogman, Martine, AuthorJia, Tianye, AuthorBurkhardt, Ralph, AuthorKlein, Marieke, AuthorCrivello, Fabrice, AuthorJanowitz, Deborah, AuthorCarmichael, Owen, AuthorHaukvik, Unn K., AuthorAribisala, Benjamin S., AuthorSchmidt, Helena, AuthorStrike, Lachlan T., AuthorCheng, Ching-Yu, AuthorRisacher, Shannon L., AuthorPuetz, Benno2, Author           Fleischman, Debra A., AuthorAssareh, Amelia A., AuthorMattay, Venkata S., AuthorBuckner, Randy L., AuthorMecocci, Patrizia, AuthorDale, Anders M., AuthorCichon, Sven, AuthorBoks, Marco P., AuthorMatarin, Mar, AuthorPenninx, Brenda W. J. H., AuthorCalhoun, Vince D., AuthorChakravarty, M. Mallar, AuthorMarquand, Andre F., AuthorMacare, Christine, AuthorMasouleh, Shahrzad Kharabian, AuthorOosterlaan, Jaap, AuthorAmouyel, Philippe, AuthorHegenscheid, Katrin, AuthorRotter I, Jerome, AuthorSchork, Andrew J., AuthorLiewald, David C. M., Authorde Zubicaray I, Greig, AuthorWong, Tien Yin, AuthorShen, Li, AuthorSaemann, Philipp G.1, Author           Brodaty, Henry, AuthorRoffman, Joshua L., Authorde Geus, Eco J. C., AuthorTsolaki, Magda, AuthorErk, Susanne, Authorvan Eijk, Kristel R., AuthorCavalleri, Gianpiero L., Authorvan der Wee, Nic J. A., AuthorMcIntosh, Andrew M., AuthorGollub, Randy L., AuthorBulayeva, Kazima B., AuthorBernard, Manon, AuthorRichards, Jennifer S., AuthorHimali, Jayandra J., AuthorLoeffler, Markus, AuthorRommelse, Nanda, AuthorHoffmann, Wolfgang, AuthorWestlye, Lars T., AuthorHernandez, Maria C. Valdes, AuthorHansell, Narelle K., Authorvan Erp, Theo G. M., AuthorWolf, Christiane, AuthorKwok, John B. J., AuthorVellas, Bruno, AuthorHeinz, Andreas, AuthorLoohuis, Loes M. Olde, AuthorDelanty, Norman, AuthorHo, Beng-Choon, AuthorChing, Christopher R. K., AuthorShumskaya, Elena, AuthorSingh, Baljeet, AuthorHofman, Albert, Authorvan der Meer, Dennis, AuthorHomuth, Georg, AuthorPsaty, Bruce M., AuthorBastin, Mark E., AuthorMontgomery, Grant W., AuthorForoud, Tatiana M., AuthorReppermund, Simone, AuthorHottenga, Jouke-Jan, AuthorSimmons, Andrew, AuthorMeyer-Lindenberg, Andreas, AuthorCahn, Wiepke, AuthorWhelan, Christopher D., Authorvan Donkelaar, Marjolein M. J., AuthorYang, Qiong, AuthorHosten, Norbert, AuthorGreen, Robert C., AuthorThalamuthu, Anbupalam, AuthorMohnke, Sebastian, AuthorPol, Hilleke E. Hulshoff, AuthorLin, Honghuang, AuthorJack Jr., Clifford R., AuthorSchofield, Peter R., AuthorMuehleisen, Thomas W., AuthorMaillard, Pauline, AuthorPotkin, Steven G., AuthorWen, Wei, AuthorFletcher, Evan, AuthorToga, Arthur W., AuthorGruber, Oliver, AuthorHuentelman, Matthew, AuthorSmith, George Davey, AuthorLauner, Lenore J., AuthorNyberg, Lars, AuthorJonsson, Erik G., AuthorCrespo-Facorro, Benedicto, AuthorKoen, Nastassja, AuthorGreve, Douglas N., AuthorUitterlinden, Andre G., AuthorWeinberger, Daniel R., AuthorSteen, Vidar M., AuthorFedko, Iryna O., AuthorGroenewold, Nynke A., AuthorNiessen, Wiro J., AuthorToro, Roberto, AuthorTzourio, Christophe, AuthorLongstreth Jr., William T., AuthorIkram, M. Kamran, AuthorSmoller, Jordan W., Authorvan Tol, Marie-Jose, AuthorSussmann, Jessika E., AuthorPaus, Tomas, AuthorLemaitre, Herve, AuthorSchroeter, Matthias L., AuthorMazoyer, Bernard, AuthorAndreassen, Ole A., AuthorHolsboer, Florian1, Author           Depondt, Chantal, AuthorVeltman, Dick J., AuthorTurner, Jessica A., AuthorPausova, Zdenka, AuthorSchumann, Gunter, Authorvan Rooij, Daan, AuthorDjurovic, Srdjan, AuthorDeary, Ian J., AuthorMcMahon, Katie L., AuthorMueller-Myhsok, Bertram2, Author           Brouwer, Rachel M., AuthorSoininen, Hilkka, AuthorPandolfo, Massimo, AuthorWassink, Thomas H., AuthorCheung, Joshua W., AuthorWolfers, Thomas, AuthorMartinot, Jean-Luc, AuthorZwiers, Marcel P., AuthorNauck, Matthias, AuthorMelle, Ingrid, AuthorMartin, Nicholas G., AuthorKanai, Ryota, AuthorWestman, Eric, AuthorKahn, Rene S., AuthorSisodiya, Sanjay M., AuthorWhite, Tonya, AuthorSaremi, Arvin, Authorvan Bokhoven, Hans, AuthorBrunner, Han G., AuthorVoelzke, Henry, AuthorWright, Margaret J., Authorvan't Ent, Dennis, AuthorNoethen, Markus M., AuthorOphoff, Roel A., AuthorBuitelaar, Jan K., AuthorFernandez, Guilln, AuthorSachdev, Perminder S., AuthorRietschel, Marcella, Authorvan Haren, Neeltje E. M., AuthorFisher, Simon E., AuthorBeiser, Alexa S., AuthorFrancks, Clyde, AuthorSaykin, Andrew J., AuthorMather, Karen A., AuthorRomanczuk-Seiferth, Nina, AuthorHartman, Catharina A., AuthorDeStefano, Anita L., AuthorHeslenfeld, Dirk J., AuthorWeiner, Michael W., AuthorWalter, Henrik, AuthorHoekstra, Pieter J., AuthorNyquist, Paul A., AuthorFranke, Barbara, AuthorBennett, David A., AuthorGrabe, Hans J., AuthorJohnson, Andrew D., AuthorChen, Christopher, Authorvan Duijn, Cornelia M., AuthorLopez, Oscar L., AuthorFornage, Myriam, AuthorWardlaw, Joanna M., AuthorSchmidt, Reinhold, AuthorDeCarli, Charles, AuthorDe Jager, Philip L., AuthorVillringer, Arno, AuthorDebette, Stephanie, AuthorGudnason, Vilmundur, AuthorMedland, Sarah E., AuthorShulman, Joshua M., AuthorThompson, Paul M., AuthorSeshadri, Sudha, AuthorIkram, M. Arfan, Author more..
Affiliations:
1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              
2RG Statistical Genetics, Max Planck Institute of Psychiatry, Max Planck Society, ou_2040288              

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 Abstract: Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

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 Dates: 2019
 Publication Status: Issued
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 Identifiers: ISI: 000494714300011
DOI: 10.1038/s41588-019-0511-y
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Title: NATURE GENETICS
Source Genre: Journal
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Pages: - Volume / Issue: 51 (11) Sequence Number: - Start / End Page: 1624 - 1636 Identifier: ISSN: 1061-4036