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  Novel genetic loci underlying human intracranial volume identified through genome-wide association

Adams, H. H. H., Hibar, D. P., Chouraki, V., Stein, J. L., Nyquist, P. A., Renteria, M. E., et al. (2016). Novel genetic loci underlying human intracranial volume identified through genome-wide association. NATURE NEUROSCIENCE, 19(12), 1569-1582. doi:10.1038/nn.4398.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-31C9-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-31CA-8
Genre: Journal Article

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 Creators:
Adams, Hieab H. H.1, Author
Hibar, Derrek P.1, Author
Chouraki, Vincent1, Author
Stein, Jason L.1, Author
Nyquist, Paul A.1, Author
Renteria, Miguel E.1, Author
Trompet, Stella1, Author
Arias-Vasquez, Alejandro1, Author
Seshadri, Sudha1, Author
Desrivieres, Sylvane1, Author
Beecham, Ashley H.1, Author
Jahanshad, Neda1, Author
Wittfeld, Katharine1, Author
Van der Lee, Sven J.1, Author
Abramovic, Lucija1, Author
Alhusaini, Saud1, Author
Amin, Najaf1, Author
Andersson, Micael1, Author
Arfanakis, Konstantinos1, Author
Aribisala, Benjamin S.1, Author
Armstrong, Nicola J.1, AuthorAthanasiu, Lavinia1, AuthorAxelsson, Tomas1, AuthorBeiser, Alexa1, AuthorBernard, Manon1, AuthorBis, Joshua C.1, AuthorBlanken, Laura M. E.1, AuthorBlanton, Susan H.1, AuthorBohlken, Marc M.1, AuthorBoks, Marco P.1, AuthorBralten, Janita1, AuthorBrickman, Adam M.1, AuthorCarmichael, Owen1, AuthorChakravarty, M. Mallar1, AuthorChauhan, Ganesh1, AuthorChen, Qiang1, AuthorChing, Christopher R. K.1, AuthorCuellar-Partida, Gabriel1, AuthorDen Braber, Anouk1, AuthorDoan, Nhat Trung1, AuthorEhrlich, Stefan1, AuthorFilippi, Irina1, AuthorGe, Tian1, AuthorGiddaluru, Sudheer1, AuthorGoldman, Aaron L.1, AuthorGottesman, Rebecca F.1, AuthorGreven, Corina U.1, AuthorGrimm, Oliver1, AuthorGriswold, Michael E.1, AuthorGuadalupe, Tulio1, AuthorHass, Johanna1, AuthorHaukvik, Unn K.1, AuthorHilal, Saima1, AuthorHofer, Edith1, AuthorHöhn, David2, Author              Holmes, Avram J.1, AuthorHoogman, Martine1, AuthorJanowitz, Deborah1, AuthorJia, Tianye1, AuthorKasperaviciute, Dalia1, AuthorKim, Sungeun1, AuthorKlein, Marieke1, AuthorKraemer, Bernd1, AuthorLee, Phil H.1, AuthorLiao, Jiemin1, AuthorLiewald, David C. M.1, AuthorLopez, Lorna M.1, AuthorLuciano, Michelle1, AuthorMacare, Christine1, AuthorMarquand, Andre1, AuthorMatarin, Mar1, AuthorMather, Karen A.1, AuthorMattheisen, Manuel1, AuthorMazoyer, Bernard1, AuthorMckay, David R.1, AuthorMcWhirter, Rebekah1, AuthorMilaneschi, Yuri1, AuthorMirza-Schreiber, Nazanin2, Author              Muetzel, Ryan L.1, AuthorManiega, Susana Munoz1, AuthorNho, Kwangsik1, AuthorNugent, Allison C.1, AuthorLoohuis, Loes M. Olde1, AuthorOosterlaan, Jaap1, AuthorPapmeyer, Martina1, AuthorPappa, Irene1, AuthorPirpamer, Lukas1, AuthorPudas, Sara1, AuthorPütz, Benno2, Author              Rajan, Kumar B.1, AuthorRamasamy, Adaikalavan1, AuthorRichards, Jennifer S.1, AuthorRisacher, Shannon L.1, AuthorRoiz-Santianez, Roberto1, AuthorRommelse, Nanda1, AuthorRose, Emma J.1, AuthorRoyle, Natalie A.1, AuthorRundek, Tatjana1, AuthorSämann, Philipp G.2, Author              Satizabal, Claudia L.1, AuthorSchmaal, Lianne1, AuthorSchork, Andrew J.1, AuthorShen, Li1, AuthorShin, Jean1, AuthorShumskaya, Elena1, AuthorSmith, Albert V.1, AuthorSprooten, Emma1, AuthorStrike, Lachlan T.1, AuthorTeumer, Alexander1, AuthorThomson, Russell1, AuthorTordesillas-Gutierrez, Diana1, AuthorToro, Roberto1, AuthorTrabzuni, Daniah1, AuthorVaidya, Dhananjay1, AuthorVan der Grond, Jeroen1, AuthorVan der Meer, Dennis1, AuthorVan Donkelaar, Marjolein M. J.1, AuthorVan Eijk, Kristel R.1, AuthorVan Erp, Theo G. M.1, AuthorVan Rooij, Daan1, AuthorWalton, Esther1, AuthorWestlye, Lars T.1, AuthorWhelan, Christopher D.1, AuthorWindham, Beverly G.1, AuthorWinkler, Anderson M.1, AuthorWoldehawariat, Girma1, AuthorWolf, Christiane1, AuthorWolfers, Thomas1, AuthorXu, Bing1, AuthorYanek, Lisa R.1, AuthorYang, Jingyun1, AuthorZijdenbos, Alex1, AuthorZwiers, Marcel P.1, AuthorAgartz, Ingrid1, AuthorAggarwal, Neelum T.1, AuthorAlmasy, Laura1, AuthorAmes, David1, AuthorAmouyel, Philippe1, AuthorAndreassen, Ole A.1, AuthorArepalli, Sampath1, AuthorAssareh, Amelia A.1, AuthorBarral, Sandra1, AuthorBastin, Mark E.1, AuthorBecker, Diane M.1, AuthorBecker, James T.1, AuthorBennett, David A.1, AuthorBlangero, John1, Authorvan Bokhoven, Hans1, AuthorBoomsma, Dorret I.1, AuthorBrodaty, Henry1, AuthorBrouwer, Rachel M.1, AuthorBrunner, Han G.1, AuthorBuckner, Randy L.1, AuthorBuitelaar, Jan K.1, AuthorBulayeva, Kazima B.1, AuthorCahn, Wiepke1, AuthorCalhoun, Vince D.1, AuthorCannon, Dara M.1, AuthorCavalleri, Gianpiero L.1, AuthorChen, Christopher1, AuthorCheng, Ching -Yu1, AuthorCichon, Sven1, AuthorCookson, Mark R.1, AuthorCorvin, Aiden1, AuthorCrespo-Facorro, Benedicto1, AuthorCurran, Joanne E.1, AuthorCzisch, Michael2, Author              Dale, Anders M.1, AuthorDavies, Gareth E.1, AuthorDe Geus, Eco J. C.1, AuthorDe Jager, Philip L.1, Authorde Zubicaray, Greig I.1, AuthorDelanty, Norman1, AuthorDepondt, Chantal1, AuthorDeStefano, Anita L.1, AuthorDillman, Allissa1, AuthorDjurovic, Srdjan1, AuthorDonohoe, Gary1, AuthorDrevets, Wayne C.1, AuthorDuggirala, Ravi1, AuthorDyer, Thomas D.1, AuthorErk, Susanne1, AuthorEspeseth, Thomas1, AuthorEvans, Denis A.1, AuthorFedko, Iryna1, AuthorFernandez, Guillen1, AuthorFerrucci, Luigi1, AuthorFisher, Simon E.1, AuthorFleischman, Debra A.1, AuthorFord, Ian1, AuthorForoud, Tatiana M.1, AuthorFox, Peter T.1, AuthorFrancks, Clyde1, AuthorFukunaga, Masaki1, AuthorGibbs, J. Raphael1, AuthorGlahn, David C.1, AuthorGollub, Randy L.1, AuthorGoring, Harald H. H.1, AuthorGrabe, Hans J.1, AuthorGreen, Robert C.1, AuthorGruber, Oliver1, AuthorGudnason, Vilmundur1, AuthorGuelfi, Sebastian1, AuthorHansell, Narelle K.1, AuthorHardy, John1, AuthorHartman, Catharina A.1, AuthorHashimoto, Ryota1, AuthorHegenscheid, Katrin1, AuthorHeinz, Andreas1, AuthorLe Hellard, Stephanie1, AuthorHernandez, Dena G.1, AuthorHeslenfeld, Dirk J.1, AuthorHo, Beng-Choon1, AuthorHoekstra, Pieter J.1, AuthorHoffmann, Wolfgang1, AuthorHofman, Albert1, AuthorHolsboer, Florian1, 3, Author              Homuth, Georg1, AuthorHosten, Norbert1, AuthorHottenga, Jouke-Jan1, AuthorPol, Hilleke E. Hulshoff1, AuthorIkeda, Masashi1, AuthorIkram, M. Kamran1, AuthorJack Jr., Clifford R.1, AuthorJenldnson, Mark1, AuthorJohnson, Robert1, AuthorJonsson, Erik G.1, AuthorJukema, J. Wouter1, AuthorKahn, Rene S.1, AuthorKanai, Ryota1, AuthorKloszewska, Iwona1, AuthorKnopman, David S.1, AuthorKochunov, Peter1, AuthorKwok, John B.1, AuthorLawrie, Stephen M.1, AuthorLemaitre, Herve1, AuthorLiu, Xinmin1, AuthorLongo, Dan L.1, AuthorLongstreth Jr., W. T.1, AuthorLopez, Oscar L.1, AuthorLovestone, Simon1, AuthorMartinez, Oliver1, AuthorMartinot, Jean-Luc1, AuthorMattay, Venkata S.1, AuthorMcDonald, Colm1, AuthorMcIntosh, Andrew M.1, AuthorMcMahon, Katie L.1, AuthorMcMahon, Francis J.1, AuthorMecocci, Patrizia1, AuthorMelle, Ingrid1, AuthorMeyer-Lindenberg, Andreas1, AuthorMohnke, Sebastian1, AuthorMontgomery, Grant W.1, AuthorMorris, Derek W.1, AuthorMosley, Thomas H.1, AuthorMuhleisen, Thomas W.1, AuthorMüller-Myhsok, Bertram1, 2, Author              Nalls, Michael A.1, AuthorNauck, Matthias1, AuthorNichols, Thomas E.1, AuthorNiessen, Wiro J.1, AuthorNoethen, Markus M.1, AuthorNyberg, Lars1, AuthorOhi, Kazutaka1, AuthorOlvera, Rene L.1, AuthorOphoff, Roel A.1, AuthorPandolfo, Massimo1, AuthorPaus, Tomas1, AuthorPausova, Zdenka1, AuthorPenninx, Brenda W. J. H.1, AuthorPike, G. Bruce1, AuthorPotkin, Steven G.1, AuthorPsaty, Bruce M.1, AuthorReppermund, Simone1, AuthorRietschel, Marcella1, AuthorRoffman, Joshua L.1, AuthorRomanczuk-Seiferth, Nina1, AuthorRotter, Jerome I.1, AuthorRyten, Mina1, AuthorSacco, Ralph L.1, AuthorSachdev, Perminder S.1, AuthorSaykin, Andrew J.1, AuthorSchmidt, Reinhold1, AuthorSchofield, Peter R.1, AuthorSigurdsson, Sigurdur1, AuthorSimmons, Andy1, AuthorSingleton, Andrew1, AuthorSisodiya, Sanjay M.1, AuthorSmith, Colin1, AuthorSmoller, Jordan W.1, AuthorSoininen, Hindu.1, AuthorSrikanth, Velandai1, AuthorSteen, Vidar M.1, AuthorStott, David J.1, AuthorSussmann, Jessika E.1, AuthorThalamuthu, Anbupalam1, AuthorTiemeier, Henning1, AuthorToga, Arthur W.1, AuthorTraynor, Bryan J.1, AuthorTroncoso, Juan1, AuthorTurner, Jessica A.1, AuthorTzourio, Christophe1, AuthorUitterlinden, Andre G.1, AuthorHernandez, Maria C. Valdes1, AuthorVan der Brug, Marcel1, AuthorVan der Lugt, Aad1, AuthorVan der Wee, Nic J. A.1, AuthorVan Duijn, Cornelia M.1, AuthorVan Haren, Neeltje E. M.1, AuthorVan't Ent, Dennis1, AuthorVan Tol, Marie Jose1, AuthorVardarajan, Badri N.1, AuthorVeltman, Dick J.1, AuthorVernooij, Meike W.1, AuthorVoelzke, Henry1, AuthorWalter, Henrik1, AuthorWardlaw, Joanna M.1, AuthorWassink, Thomas H.1, AuthorWeale, Michael E.1, AuthorWeinberger, Daniel R.1, AuthorWeiner, Michael W.1, AuthorWen, Wei1, AuthorWestman, Eric1, AuthorWhite, Tonya1, AuthorWong, Tien Y.1, AuthorWright, Clinton B.1, AuthorZielke, H. Ronald1, AuthorZonderman, Alan B.1, AuthorDeary, Ian J.1, AuthorDeCarli, Charles1, AuthorSchmidt, Helena1, AuthorMartin, Nicholas G.1, AuthorDe Craen, Anton J. M.1, AuthorWright, Margaret J.1, AuthorLauner, Lenore J.1, AuthorSchumann, Gunter1, AuthorFornage, Myriam1, AuthorFranke, Barbara1, AuthorDebette, Stephanie1, AuthorMedland, Sarah E.1, AuthorIkram, M. Arfan1, AuthorThompson, Paul M.1, Author more..
Affiliations:
1external, ou_persistent22              
2Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              
3Emeritiertes wissenschaftliches Mitglied, Max Planck Institute of Psychiatry, Max Planck Society, ou_2074301              

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 Abstract: Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

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Language(s): eng - English
 Dates: 2016-12
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: ISI: 000389011900016
DOI: 10.1038/nn.4398
 Degree: -

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Title: NATURE NEUROSCIENCE
Source Genre: Journal
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Pages: - Volume / Issue: 19 (12) Sequence Number: - Start / End Page: 1569 - 1582 Identifier: ISSN: 1097-6256