Genetic architecture of subcortical brain structures in 38,851 individuals

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 id... Mehr ...

Verfasser: Satizabal, Claudia L
Adams, Hieab H H
Hibar, Derrek P
White, Charles C
Knol, Maria J
Stein, Jason L
Scholz, Markus
Sargurupremraj, Muralidharan
Jahanshad, Neda
Roshchupkin, Gennady V
Smith, Albert V
Bis, Joshua C
Jian, Xueqiu
Luciano, Michelle
Hofer, Edith
Teumer, Alexander
van der Lee, Sven J
Yang, Jingyun
Yanek, Lisa R
Lee, Tom V
Li, Shuo
Hu, Yanhui
Koh, Jia Yu
Eicher, John D
Desrivières, Sylvane
Arias-Vasquez, Alejandro
Chauhan, Ganesh
Athanasiu, Lavinia
Rentería, Miguel E
Kim, Sungeun
Hoehn, David
Armstrong, Nicola J
Chen, Qiang
Holmes, Avram J
den Braber, Anouk
Kloszewska, Iwona
Andersson, Micael
Espeseth, Thomas
Grimm, Oliver
Abramovic, Lucija
Alhusaini, Saud
Milaneschi, Yuri
Papmeyer, Martina
Axelsson, Tomas
Ehrlich, Stefan
Roiz-Santiañez, Roberto
Kraemer, Bernd
Håberg, Asta K
Jones, Hannah J
Pike, G Bruce
Stein, Dan J
Stevens, Allison
Bralten, Janita
Vernooij, Meike W
Harris, Tamara B
Filippi, Irina
Witte, A Veronica
Guadalupe, Tulio
Wittfeld, Katharina
Mosley, Thomas H
Becker, James T
Doan, Nhat Trung
Hagenaars, Saskia P
Saba, Yasaman
Cuellar-Partida, Gabriel
Amin, Najaf
Hilal, Saima
Nho, Kwangsik
Mirza-Schreiber, Nazanin
Arfanakis, Konstantinos
Becker, Diane M
Ames, David
Goldman, Aaron L
Lee, Phil H
Boomsma, Dorret I
Lovestone, Simon
Giddaluru, Sudheer
Le Hellard, Stephanie
Mattheisen, Manuel
Bohlken, Marc M
Kasperaviciute, Dalia
Schmaal, Lianne
Lawrie, Stephen M
Agartz, Ingrid
Walton, Esther
Tordesillas-Gutierrez, Diana
Davies, Gareth E
Shin, Jean
Ipser, Jonathan C
Vinke, Louis N
Hoogman, Martine
Jia, Tianye
Burkhardt, Ralph
Klein, Marieke
Crivello, Fabrice
Janowitz, Deborah
Carmichael, Owen
Haukvik, Unn K
Aribisala, Benjamin S
Schmidt, Helena
Strike, Lachlan T
Cheng, Ching-Yu
Risacher, Shannon L
Pütz, Benno
Fleischman, Debra A
Assareh, Amelia A
Mattay, Venkata S
Buckner, Randy L
Mecocci, Patrizia
Dale, Anders M
Cichon, Sven
Boks, Marco P
Matarin, Mar
Penninx, Brenda W J H
Calhoun, Vince D
Chakravarty, M Mallar
Marquand, Andre F
Macare, Christine
Kharabian Masouleh, Shahrzad
Oosterlaan, Jaap
Amouyel, Philippe
Hegenscheid, Katrin
Rotter, Jerome I
Schork, Andrew J
Liewald, David C M
de Zubicaray, Greig I
Wong, Tien Yin
Shen, Li
Sämann, Philipp G
Brodaty, Henry
Roffman, Joshua L
de Geus, Eco J C
Tsolaki, Magda
Erk, Susanne
van Eijk, Kristel R
Cavalleri, Gianpiero L
van der Wee, Nic J A
McIntosh, Andrew M
Gollub, Randy L
Bulayeva, Kazima B
Bernard, Manon
Richards, Jennifer S
Himali, Jayandra J
Loeffler, Markus
Rommelse, Nanda
Hoffmann, Wolfgang
Westlye, Lars T
Valdés Hernández, Maria C
Hansell, Narelle K
van Erp, Theo G M
Wolf, Christiane
Kwok, John B J
Vellas, Bruno
Heinz, Andreas
Olde Loohuis, Loes M
Delanty, Norman
Ho, Beng-Choon
Ching, Christopher R K
Shumskaya, Elena
Singh, Baljeet
Hofman, Albert
van der Meer, Dennis
Homuth, Georg
Psaty, Bruce M
Bastin, Mark E
Montgomery, Grant W
Foroud, Tatiana M
Reppermund, Simone
Hottenga, Jouke-Jan
Simmons, Andrew
Meyer-Lindenberg, Andreas
Cahn, Wiepke
Whelan, Christopher D
van Donkelaar, Marjolein M J
Yang, Qiong
Hosten, Norbert
Green, Robert C
Thalamuthu, Anbupalam
Mohnke, Sebastian
Hulshoff Pol, Hilleke E
Lin, Honghuang
Jack, Clifford R
Schofield, Peter R
Mühleisen, Thomas W
Maillard, Pauline
Potkin, Steven G
Wen, Wei
Fletcher, Evan
Toga, Arthur W
Gruber, Oliver
Huentelman, Matthew
Davey Smith, George
Launer, Lenore J
Nyberg, Lars
Jönsson, Erik G
Crespo-Facorro, Benedicto
Koen, Nastassja
Greve, Douglas N
Uitterlinden, André G
Weinberger, Daniel R
Steen, Vidar M
Fedko, Iryna O
Groenewold, Nynke A
Niessen, Wiro J
Toro, Roberto
Tzourio, Christophe
Longstreth, William T
Ikram, M Kamran
Smoller, Jordan W
van Tol, Marie-Jose
Sussmann, Jessika E
Paus, Tomas
Lemaître, Hervé
Schroeter, Matthias L
Mazoyer, Bernard
Andreassen, Ole A
Holsboer, Florian
Depondt, Chantal
Veltman, Dick J
Turner, Jessica A
Pausova, Zdenka
Schumann, Gunter
van Rooij, Daan
Djurovic, Srdjan
Deary, Ian J
McMahon, Katie L
Müller-Myhsok, Bertram
Brouwer, Rachel M
Soininen, Hilkka
Pandolfo, Massimo
Wassink, Thomas H
Cheung, Joshua W
Wolfers, Thomas
Martinot, Jean-Luc
Zwiers, Marcel P
Nauck, Matthias
Melle, Ingrid
Martin, Nicholas G
Kanai, Ryota
Westman, Eric
Kahn, René S
Sisodiya, Sanjay M
White, Tonya
Saremi, Arvin
van Bokhoven, Hans
Brunner, Han G
Völzke, Henry
Wright, Margaret J
van 't Ent, Dennis
Nöthen, Markus M
Ophoff, Roel A
Buitelaar, Jan K
Fernández, Guillén
Sachdev, Perminder S
Rietschel, Marcella
van Haren, Neeltje E M
Fisher, Simon E
Beiser, Alexa S
Francks, Clyde
Saykin, Andrew J
Mather, Karen A
Romanczuk-Seiferth, Nina
Hartman, Catharina A
DeStefano, Anita L
Heslenfeld, Dirk J
Weiner, Michael W
Walter, Henrik
Hoekstra, Pieter J
Nyquist, Paul A
Franke, Barbara
Bennett, David A
Grabe, Hans J
Johnson, Andrew D
Chen, Christopher
van Duijn, Cornelia M
Lopez, Oscar L
Fornage, Myriam
Wardlaw, Joanna M
Schmidt, Reinhold
DeCarli, Charles
De Jager, Philip L
Villringer, Arno
Debette, Stéphanie
Gudnason, Vilmundur
Medland, Sarah E
Shulman, Joshua M
Thompson, Paul M
Seshadri, Sudha
Ikram, M Arfan
Dokumenttyp: Artikel
Erscheinungsdatum: 2019
Reihe/Periodikum: Satizabal , C L , Adams , H H H , Hibar , D P , White , C C , Knol , M J , Stein , J L , Scholz , M , Sargurupremraj , M , Jahanshad , N , Roshchupkin , G V , Smith , A V , Bis , J C , Jian , X , Luciano , M , Hofer , E , Teumer , A , van der Lee , S J , Yang , J , Yanek , L R , Lee , T V , Li , S , Hu , Y , Koh , J Y , Eicher , J D , Desrivières , S , Arias-Vasquez , A , Chauhan , G , Athanasiu , L , Rentería , M E , Kim , S , Hoehn , D , Armstrong , N J , Chen , Q , Holmes , A J , den Braber , A , Kloszewska , I , Andersson , M , Espeseth , T , Grimm , O , Abramovic , L , Alhusaini , S , Milaneschi , Y , Papmeyer , M , Axelsson , T , Ehrlich , S , Roiz-Santiañez , R , Kraemer , B , Håberg , A K , Jones , H J , Pike , G B , Stein , D J , Stevens , A , Bralten , J , Vernooij , M W , Harris , T B , Filippi , I , Witte , A V , Guadalupe , T , Wittfeld , K , Mosley , T H , Becker , J T , Doan , N T , Hagenaars , S P , Saba , Y , Cuellar-Partida , G , Amin , N , Hilal , S , Nho , K , Mirza-Schreiber , N , Arfanakis , K , Becker , D M , Ames , D , Goldman , A L , Lee , P H , Boomsma , D I , Lovestone , S , Giddaluru , S , Le Hellard , S , Mattheisen , M , Bohlken , M M , Kasperaviciute , D , Schmaal , L , Lawrie , S M , Agartz , I , Walton , E , Tordesillas-Gutierrez , D , Davies , G E , Shin , J , Ipser , J C , Vinke , L N , Hoogman , M , Jia , T , Burkhardt , R , Klein , M , Crivello , F , Janowitz , D , Carmichael , O , Haukvik , U K , Aribisala , B S , Schmidt , H , Strike , L T , Cheng , C-Y , Risacher , S L , Pütz , B , Fleischman , D A , Assareh , A A , Mattay , V S , Buckner , R L , Mecocci , P , Dale , A M , Cichon , S , Boks , M P , Matarin , M , Penninx , B W J H , Calhoun , V D , Chakravarty , M M , Marquand , A F , Macare , C , Kharabian Masouleh , S , Oosterlaan , J , Amouyel , P , Hegenscheid , K , Rotter , J I , Schork , A J , Liewald , D C M , de Zubicaray , G I , Wong , T Y , Shen , L , Sämann , P G , Brodaty , H , Roffman , J L , de Geus , E J C , Tsolaki , M , Erk , S , van Eijk , K R , Cavalleri , G L , van der Wee , N J A , McIntosh , A M , Gollub , R L , Bulayeva , K B , Bernard , M , Richards , J S , Himali , J J , Loeffler , M , Rommelse , N , Hoffmann , W , Westlye , L T , Valdés Hernández , M C , Hansell , N K , van Erp , T G M , Wolf , C , Kwok , J B J , Vellas , B , Heinz , A , Olde Loohuis , L M , Delanty , N , Ho , B-C , Ching , C R K , Shumskaya , E , Singh , B , Hofman , A , van der Meer , D , Homuth , G , Psaty , B M , Bastin , M E , Montgomery , G W , Foroud , T M , Reppermund , S , Hottenga , J-J , Simmons , A , Meyer-Lindenberg , A , Cahn , W , Whelan , C D , van Donkelaar , M M J , Yang , Q , Hosten , N , Green , R C , Thalamuthu , A , Mohnke , S , Hulshoff Pol , H E , Lin , H , Jack , C R , Schofield , P R , Mühleisen , T W , Maillard , P , Potkin , S G , Wen , W , Fletcher , E , Toga , A W , Gruber , O , Huentelman , M , Davey Smith , G , Launer , L J , Nyberg , L , Jönsson , E G , Crespo-Facorro , B , Koen , N , Greve , D N , Uitterlinden , A G , Weinberger , D R , Steen , V M , Fedko , I O , Groenewold , N A , Niessen , W J , Toro , R , Tzourio , C , Longstreth , W T , Ikram , M K , Smoller , J W , van Tol , M-J , Sussmann , J E , Paus , T , Lemaître , H , Schroeter , M L , Mazoyer , B , Andreassen , O A , Holsboer , F , Depondt , C , Veltman , D J , Turner , J A , Pausova , Z , Schumann , G , van Rooij , D , Djurovic , S , Deary , I J , McMahon , K L , Müller-Myhsok , B , Brouwer , R M , Soininen , H , Pandolfo , M , Wassink , T H , Cheung , J W , Wolfers , T , Martinot , J-L , Zwiers , M P , Nauck , M , Melle , I , Martin , N G , Kanai , R , Westman , E , Kahn , R S , Sisodiya , S M , White , T , Saremi , A , van Bokhoven , H , Brunner , H G , Völzke , H , Wright , M J , van 't Ent , D , Nöthen , M M , Ophoff , R A , Buitelaar , J K , Fernández , G , Sachdev , P S , Rietschel , M , van Haren , N E M , Fisher , S E , Beiser , A S , Francks , C , Saykin , A J , Mather , K A , Romanczuk-Seiferth , N , Hartman , C A , DeStefano , A L , Heslenfeld , D J , Weiner , M W , Walter , H , Hoekstra , P J , Nyquist , P A , Franke , B , Bennett , D A , Grabe , H J , Johnson , A D , Chen , C , van Duijn , C M , Lopez , O L , Fornage , M , Wardlaw , J M , Schmidt , R , DeCarli , C , De Jager , P L , Villringer , A , Debette , S , Gudnason , V , Medland , S E , Shulman , J M , Thompson , P M , Seshadri , S & Ikram , M A 2019 , ' Genetic architecture of subcortical brain structures in 38,851 individuals ' , Nature Genetics , vol. 51 , no. 11 , pp. 1624-1636 . https://doi.org/10.1038/s41588-019-0511-y
Schlagwörter: /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_ / name=Netherlands Twin Register (NTR) / /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being / name=SDG 3 - Good Health and Well-being
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29214048
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://research.vu.nl/en/publications/78126867-921a-42a4-9782-e8522f6ba4d4

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.