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  Genetic architecture of subcortical brain structures in 38,851 individuals

Satizabal, C. L., Adams, H. H. H., Hibar, D., White, C. C., Stein, J. L., Scholz, M., et al. (2019). Genetic architecture of subcortical brain structures in 38,851 individuals. Nature Genetics, 51, 1624-1635. doi:10.1038/s41588-019-0511-y.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0004-C26A-A Version Permalink: https://hdl.handle.net/21.11116/0000-000D-A1A8-F
Genre: Journal Article

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055269/ (Preprint)
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 Creators:
Satizabal, Claudia L.1, Author
Adams, Hieab H. H. 1, Author
Hibar, Derrek 1, Author
White, Charles C.1, Author
Stein, Jason L.1, Author
Scholz, Markus 1, Author
Sargurupremraj, Murali 1, Author
Jahanshad, Neda 1, Author
Smith, Albert V.1, Author
Bis, Joshua C.1, Author
Jian, Xueqiu 1, Author
Luciano, Michelle 1, Author
Hofer, Edith 1, Author
Teumer, Alexander1, Author
van der Lee, Sven J.1, Author
Yang, Jingyun1, Author
Yanek, Lisa R.1, Author
Lee, Tom V.1, Author
Li, Shuo 1, Author
Hu, Yanhui 1, Author
Koh, Jia Yu 1, AuthorEicher, John D.1, AuthorDesrivières, Sylvane 1, AuthorArias-Vasquez, Alejandro 1, AuthorChauhan, Ganesh1, AuthorAthanasiu, Lavinia 1, AuthorRenteria, Miguel E.1, AuthorKim, Sungeun1, AuthorHöhn, David 1, AuthorArmstrong, Nicola J.1, AuthorChen, Qiang 1, AuthorHolmes, Avram J.1, Authorden Braber, Anouk 1, AuthorKloszewska, Iwona 1, AuthorAndersson, Micael 1, AuthorEspeseth, Thomas 1, AuthorGrimm, Oliver 1, AuthorAbramovic, Lucija 1, AuthorAlhusaini, Saud 1, AuthorMilaneschi, Yuri 1, AuthorPapmeyer, Martina 1, AuthorAxelsson, Tomas 1, AuthorEhrlich, Stefan1, AuthorRoiz-Santiañez, Roberto 1, AuthorKraemer, Bernd 1, AuthorHåberg, Asta K.1, AuthorJones, Hannah J.1, AuthorPike, G. Bruce 1, AuthorStein, Dan J.1, AuthorStevens, Allison 1, AuthorBralten, Janita 1, AuthorVernooij, Meike W.1, AuthorHarris, Tamara B.1, AuthorFilippi, Irina 1, AuthorWitte, A. Veronica1, 2, Author           Guadalupe, Tulio 1, AuthorWittfeld, Katharina 1, AuthorMosley, Thomas H.1, AuthorBecker, James T.1, AuthorDoan, Nhat Trung 1, AuthorHagenaars, Saskia P.1, AuthorSaba, Yasaman 1, AuthorCuellar-Partida, Gabriel 1, AuthorAmin, Najaf1, AuthorHilal, Saima 1, AuthorNho, Kwangsik 1, AuthorKarbalai, Nazanin 1, AuthorArfanakis, Konstantinos 1, AuthorBecker, Diane M.1, AuthorAmes, David 1, AuthorGoldman, Aaron L.1, AuthorLee, Phil H.1, AuthorBoomsma, Dorret I.1, AuthorLovestone, Simon 1, AuthorGiddaluru, Sudheer 1, AuthorLe Hellard, Stephanie 1, AuthorMattheisen, Manuel 1, AuthorBohlken, Marc M.1, AuthorKasperaviciute, Dalia1, AuthorSchmaal, Lianne 1, AuthorLawrie, Stephen M.1, AuthorAgartz, Ingrid 1, AuthorWalton, Esther 1, AuthorTordesillas-Gutierrez, Diana 1, AuthorDavies, Gareth E.1, AuthorShin, Jean 1, AuthorIpser, Jonathan C.1, AuthorVinke, Louis N.1, AuthorHoogman, Martine 1, AuthorKnol, Maria J.1, AuthorJia, Tianye 1, AuthorBurkhardt, Ralph 1, AuthorKlein, Marieke 1, AuthorCrivello, Fabrice 1, AuthorJanowitz, Deborah 1, AuthorCarmichael, Owen1, AuthorHaukvik, Unn K.1, AuthorAribisala, Benjamin S.1, AuthorSchmidt, Helena 1, AuthorStrike, Lachlan T.1, AuthorCheng, Ching-Yu 1, AuthorRisacher, Shannon L.1, AuthorPütz, Benno 1, AuthorFleischman, Debra A.1, AuthorAssareh, Amelia A.1, AuthorMattay, Venkata S.1, AuthorBuckner, Randy L.1, AuthorMecocci, Patrizia 1, AuthorDale, Anders M.1, AuthorCichon, Sven 1, AuthorBoks, Marco P.1, AuthorMatarin, Mar 1, AuthorPenninx, Brenda W. J. H. 1, AuthorCalhoun, Vince D.1, AuthorChakravarty, M. Mallar 1, AuthorMarquand, Andre 1, AuthorMacare, Christine 1, AuthorMasouleh, Shahrzad Kharabian 1, AuthorOosterlaan, Jaap 1, AuthorAmouyel, Philippe 1, AuthorHegenscheid, Katrin1, AuthorRotter, Jerome I.1, AuthorSchork, Andrew J.1, AuthorLiewald, David C. M.1, AuthorDe Zubicaray, Greig I.1, AuthorWong, Tien Yin 1, AuthorShen , Li 1, AuthorSämann, Philipp G.1, AuthorBrodaty, Henry 1, AuthorRoffman, Joshua L.1, AuthorDe Geus, Eco J. C. 1, AuthorTsolaki, Magda 1, AuthorErk, Susanne 1, AuthorVan Eijk, Kristel R.1, AuthorCavalleri, Gianpiero L.1, AuthorVan der Wee, Nic J. A. 1, AuthorMcIntosh, Andrew M.1, AuthorGollub, Randy L.1, AuthorBulayeva, Kazima B.1, AuthorBernard, Manon 1, AuthorRichards, Jennifer S.1, AuthorHimali, Jayandra J.1, AuthorLoefflel, Markus 1, AuthorRommelse, Nanda 1, AuthorHoffmann, Wolfgang 1, AuthorWestlye, Lars T.1, AuthorValdés Hernández, Maria C.1, AuthorHansell, Narelle K.1, AuthorVan Erp, Theo G. M.1, AuthorWolf, Christiane 1, AuthorKwok, John B. J.1, AuthorVellas, Bruno 1, AuthorHeinz, Andreas 1, AuthorOlde Loohuis, Loes M.1, AuthorDelanty, Norman 1, AuthorHo, Beng-Choon 1, AuthorChing, Christopher R. K.1, AuthorShumskaya, Elena 1, AuthorHofman, Albert 1, AuthorVan der Meer, Dennis 1, AuthorHomuth, Georg 1, AuthorPsaty, Bruce M.1, AuthorBastin, Mark 1, AuthorMontgomery, Grant W.1, AuthorForoud, Tatiana M.1, AuthorReppermund, Simone 1, AuthorHottenga, Jouke-Jan 1, AuthorSimmons, Andrew 1, AuthorMeyer-Lindenberg, Andreas 1, AuthorCahn, Wiepke 1, AuthorWhelan, Christopher D.1, AuthorVan Donkelaar, Marjolein M. J.1, AuthorYang, Qiong 1, AuthorHosten, Norbert 1, AuthorGreen, Robert C.1, AuthorThalamuthu, Anbupalam 1, AuthorMohnke, Sebastian1, AuthorHulshoff Pol, Hilleke E.1, AuthorLin, Honghuang 1, AuthorJack Jr., Clifford R.1, AuthorSchofield, Peter R.1, AuthorMühleisen, Thomas W.1, AuthorMaillard, Pauline 1, AuthorPotkin, Steven G.1, AuthorWen, Wei 1, AuthorFletcher, Evan 1, AuthorToga, Arthur W.1, AuthorGruber, Oliver 1, AuthorHuentelman, Matthew 1, AuthorSmith, George Davey 1, AuthorLauner, Lenore J.1, AuthorNyberg, Lars 1, AuthorJönsson, Erik G.1, AuthorCrespo-Facorro, Benedicto 1, AuthorKoen, Nastassja 1, AuthorGreve, Douglas 1, AuthorUitterlinden, André G.1, AuthorWeinberger, Daniel R.1, AuthorSteen, Vidar M.1, AuthorFedko, Iryna O.1, AuthorGroenewold, Nynke A.1, AuthorNiessen, Wiro J.1, AuthorToro, Roberto 1, AuthorTzourio, Christophe 1, AuthorLongstreth Jr., William T.1, AuthorIkram, M. Kamran 1, AuthorSmoller, Jordan W. 1, AuthorVan Tol, Marie-Jose 1, AuthorSussmann, Jessika E.1, AuthorPaus, Tomas 1, AuthorLemaître, Hervé 1, AuthorMazoyer, Bernard 1, AuthorAndreassen, Ole A.1, AuthorHolsboer, Florian1, AuthorVeltman, Dick J.1, AuthorTurner, Jessica A.1, AuthorPausova, Zdenka 1, AuthorSchumann, Gunter 1, AuthorVan Rooij, Daan 1, AuthorDjurovic, Srdjan 1, AuthorDeary, Ian J.1, AuthorMcMahon, Katie L.1, AuthorMüller-Myhsok, Bertram 1, AuthorBrouwer, Rachel M.1, AuthorSoininen, Hilkka 1, AuthorPandolfo, Massimo 1, AuthorWassink, Thomas H.1, AuthorCheung, Joshua W.1, AuthorWolfers, Thomas 1, AuthorMartinot, Jean-Luc 1, AuthorZwiers, Marcel P.1, AuthorNauck, Matthias 1, AuthorMelle, Ingrid1, AuthorMartin, Nicholas G.1, AuthorKanai, Ryota 1, AuthorWestman, Eric 1, AuthorKahn, René S.1, AuthorSisodiya, Sanjay M.1, AuthorWhite, Tonya 1, AuthorSaremi, Arvin 1, Authorvan Bokhoven, Hans 1, AuthorBrunner, Han G.1, AuthorVölzke, Henry 1, AuthorWright, Margaret J.1, AuthorVan't Ent, Dennis 1, AuthorNöthen, Markus M.1, AuthorOphoff, Roel A.1, AuthorBuitelaar, Jan K.1, AuthorFernández, Guillén1, AuthorSachdev, Perminder S.1, AuthorRietschel, Marcella 1, AuthorVan Haren, Neeltje E. M. 1, AuthorFisher, Simon E.1, AuthorBeiser, Alexa S.1, AuthorFrancks, Clyde 1, AuthorSaykin, Andrew J.1, AuthorMather, Karen A.1, AuthorRomanczuk-Seiferth, Nina 1, AuthorHartman, Catharina A.1, AuthorDeStefano, Anita L.1, AuthorHeslenfeld, Dirk J.1, AuthorWeiner, Michael W.1, AuthorWalter, Henrik 1, AuthorHoekstra, Pieter J.1, AuthorNyquist, Paul A.1, AuthorFranke, Barbara 1, AuthorBennett, David A.1, AuthorGrabe, Hans J.1, AuthorJohnson, Andrew D.1, AuthorChen, Christopher 1, Authorvan Duijn, Cornelia M.1, AuthorLopez, Oscar L.1, AuthorFornage, Myriam 1, AuthorWardlaw, Joanna A.1, AuthorSchmidt, Reinhold 1, AuthorDeCarli, Charles1, AuthorDe Jager, Philip L.1, AuthorVillringer, Arno1, 2, Author           Debette, Stéphanie 1, AuthorGudnason, Vilmundur 1, AuthorMedland, Sarah E.1, AuthorShulman, Joshua M.1, AuthorThompson, Paul M.1, AuthorSeshadri, Sudha 1, AuthorIkram, M. Arfan1, Author more..
Affiliations:
1External Organizations, ou_persistent22              
2Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

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Free keywords: Adult; Aged; Animals; Brain; Cohort Studies; Drosophila melanogaster; Genetic Variation; Genome-Wide Association Study; Humans; Magnetic Resonance Imaging; Middle Aged; Neurodevelopmental Disorders; Organ Size
 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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Language(s): eng - English
 Dates: 2017-09-262019-09-052019-10-212019-11
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41588-019-0511-y
Other: epub 2019
PMID: 31636452
 Degree: -

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Title: Nature Genetics
  Other : Nature Genet.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York, NY : Nature America, Inc.
Pages: - Volume / Issue: 51 Sequence Number: - Start / End Page: 1624 - 1635 Identifier: ISSN: 1061-4036
CoNE: https://pure.mpg.de/cone/journals/resource/954925598609