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  Novel genetic loci associated with hippocampal volume

Hibar, D. P., Adams, H. H. H., Jahanshad, N., Chauhan, G., Stein, J. L., Hofer, E., et al. (2017). Novel genetic loci associated with hippocampal volume. Nature Communications, 8: 13624. doi:10.1038/ncomms13624.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002B-A1BC-7 Version Permalink: https://hdl.handle.net/21.11116/0000-0001-1B85-B
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 Creators:
Hibar, Derrek P.1, Author
Adams, Hieab H. H.2, 3, Author
Jahanshad, Neda1, Author
Chauhan, Ganesh4, Author
Stein, Jason L.5, Author
Hofer, Edith6, 7, Author
Rentería, Miguel E.8, Author
Bis, Joshua C.9, Author
Arias-Vasquez, Alejandro10, 11, 12, 13, Author
Ikram, M. Kamran2, 14, 15, 16, 17, Author
Desrivieres, Sylvane18, Author
Vernooij, Meike W.2, 3, Author
Abramovic, Lucija19, Author
Alhusaini, Saud20, 21, Author
Amin, Najaf2, Author
Andersson, Micael22, Author
Arfanakis, Konstantinos23, 24, 25, Author
Aribisala, Benjamin S.26, 27, Author
Armstrong, Nicola J., Author
Athanasiu, Lavinia, Author
Axelsson, Tomas, AuthorBeecham, Ashley H., AuthorBeiser, Alexa, AuthorBernard, Manon, AuthorBlanton, Susan H., AuthorBohlken, Marc M.19, AuthorBoks, Marco P.19, AuthorBralten, Janita10, 13, AuthorBrickman, Adam M., AuthorCarmichael, Owen, AuthorChakravarty, M. Mallar, AuthorChen, Qiang, AuthorChing, Christopher R. K.1, AuthorChouraki, Vincent, AuthorCuellar-Partida, Gabriel8, AuthorCrivello, Fabrice, Authorden Brabander, Anouk, AuthorDoan, Nhat Trung, AuthorEhrlich, Stefan, AuthorGiddaluru, Sudheer, AuthorGoldman, Aaron L., AuthorGottesman, Rebecca F., AuthorGrimm, Oliver, AuthorGriswold, Michael E., AuthorGuadalupe, Tulio28, Author           Gutman, Boris A.1, AuthorHass, Johanna, AuthorHaukvik, Unn K., AuthorHoehn, David, AuthorHolmes, Avram J., AuthorHoogman, Martine10, 13, AuthorJanowitz, Deborah, AuthorJia, Tianye18, AuthorJørgensen, Kjetil N., AuthorMirza-Schreiber, Nazanin, AuthorKasperaviciute, Dalia, AuthorKim, Sungeun, AuthorKlein, Marieke10, 13, AuthorKrämer, Bernd, AuthorLee, Phil H., AuthorLiewald, David C. M. , AuthorLopez, Lorna M., AuthorLuciano, Michelle, AuthorMacare, Christine18, AuthorMarquand, Andre F.13, AuthorMatarin, Mar, AuthorMather, Karen A., AuthorMattheisen, Manuel, AuthorMcKay, David R., AuthorMilaneschi, Yuri, AuthorManiega, Susana Muñoz26, AuthorNho, Kwangsik, AuthorNugent, Allison C., AuthorNyquist, Paul, AuthorOlde Loohuis, Loes M., AuthorOosterlaan, Jaap, AuthorPapmeyer, Martina, AuthorPirpamer, Lukas6, AuthorPütz, Benno, AuthorRamasamy, Adaikalavan, AuthorRichards, Jennifer S.12, 13, AuthorRisacher, Shannon, AuthorRoiz-Santiañez, Roberto, AuthorRommelse, Nanda11, 13, AuthorRopele, Stefan6, AuthorRose, Emma, AuthorRoyle, Natalie A.26, AuthorRundek, Tatjana, AuthorSämann, Philipp G., AuthorSaremi, Arvin1, AuthorSatizabal, Claudia L., AuthorSchmaal, Lianne, AuthorSchork, Andrew J., AuthorShen, Li, AuthorShin, Jean, AuthorShumskaya, Elena10, 13, AuthorSmith, Albert V., AuthorSprooten, Emma, AuthorStrike, Lachlan T.8, AuthorTeumer, Alexander, AuthorTordesillas-Gutierrez, Diana, AuthorToro, Roberto, AuthorTrabzuni, Daniah, AuthorTrompet, Stella, AuthorVaidya, Dhananjay, AuthorVan der Grond, Jeroen, AuthorVan der Lee, Sven J.2, AuthorVan der Meer, Dennis, AuthorVan Donkelaar, Marjolein M. J. 10, 13, AuthorVan Eijk, Kristel R., Authorvan Erp, Theo G. M., AuthorVan Rooij, Daan 12, 13, AuthorWalton, Esther, AuthorWestlye, Lars Tjelta, AuthorWhelan, Christopher D.1, 21, AuthorWindham, Beverly G., AuthorWinkler, Anderson M., AuthorWittfeld, Katharina M., AuthorWoldehawariat, Girma, AuthorWolf, Christiane, AuthorWolfers, Thomas10, 13, AuthorYanek, Lisa R., AuthorYang, Jingyun24, AuthorZijdenbos, Alex, AuthorZwiers, Marcel P.13, AuthorAgartz, Ingrid, AuthorAlmasy, Laura, AuthorAmes, David, AuthorAmouyel, Philippe, AuthorAndreassen, Ole A., AuthorArepalli, Sampath, AuthorAssareh, Amelia A., AuthorBarral, Sandra, AuthorBastin, Mark E.26, AuthorBecker, Diane M., AuthorBecker, James T., AuthorBennett, David A.24, AuthorBlangero, John, AuthorVan Bokhoven, Hans10, 13, AuthorBoomsma, Dorret I., AuthorBrodaty, Henry , AuthorBrouwer, Rachel M.19, AuthorBrunner, Han G.10, 13, AuthorBuckner, Randy L., AuthorBuitelaar, Jan K.12, 13, AuthorBulayeva, Kazima B., AuthorCahn, Wiepke19, AuthorCalhoun, Vince D., AuthorCannon, Dara M., AuthorCavalleri, Gianpiero L.21, AuthorCheng, Ching-Yu14, 15, AuthorCichon, Sven, AuthorCookson, Mark R., AuthorCorvin, Aiden, AuthorCrespo-Facorro, Benedicto, AuthorCurran, Joanne E., AuthorCzisch, Michael, AuthorDale, Anders M., AuthorDavies, Gareth E., AuthorDe Craen, Anton J. M. , AuthorDe Geus, Eco J. C., AuthorDe Jager, Philip L., AuthorDe Zubicaray, Greig i., AuthorDeary, Ian J., AuthorDebette, Stéphanie4, AuthorDeCarli, Charles, AuthorDelanty, Norman21, AuthorDepondt, Chantal, AuthorDeStefano, Anita, AuthorDillman, Allissa, AuthorDjurovic, Srdjan, AuthorDonohoe, Gary, AuthorDrevets, Wayne C., AuthorDuggirala, Ravi, AuthorDyer, Thomas D., AuthorEnzinger, Christian6, AuthorErk, Susanne, AuthorEspeseth, Thomas, AuthorFedko, Iryna O., AuthorFernández, Guillén12, 13, AuthorFerrucci, Luigi, AuthorFisher, Simon E.13, 28, Author           Fleischman, Debra A.24, AuthorFord, Ian, AuthorFornage, Myriam, AuthorForoud, Tatiana M., AuthorFox, Peter T., AuthorFrancks, Clyde13, 28, Author           Fukunaga, Masaki, AuthorGibbs, J. Raphael, AuthorGlahn, David C., AuthorGollub, Randy L., AuthorGöring, Harald H. H., AuthorGreen, Robert C., AuthorGruber, Oliver, AuthorGudnason, Vilmundur, AuthorGuelfi, Sebastien, AuthorHaberg, Asta K., AuthorHansell, Narelle K.8, AuthorHardy, John, AuthorHartman, Catharina A., AuthorHashimoto, Ryota, AuthorHegenscheid, Katrin, AuthorHeinz, Andreas, AuthorLe Hellard , Stephanie, AuthorHernandez, Dena G., AuthorHeslenfeld, Dirk J., AuthorHo, Beng-Choon, AuthorHoekstra, Pieter J., AuthorHoffmann, Wolfgang, AuthorHofman, Albert, AuthorHolsboer, Florian, AuthorHomuth, Georg, AuthorHosten, Norbert, AuthorHottenga, Jouke-Jan, AuthorHuentelman, Matthew, AuthorPol, Hilleke E. Hulshoff19, AuthorIkeda, Masashi, AuthorJack Jr., Clifford R., AuthorJenkinson, Mark, AuthorJohnson, Robert, AuthorJonsson, Erik G., AuthorJukema, J. Wouter, AuthorKahn, Rene S.19, AuthorKanai, Ryota, AuthorKloszewska, Iwona, AuthorKnopman, David S., AuthorKochunov, Peter, AuthorKwok, John B., AuthorLawrie, Stephen M., AuthorLemaître, Hervé , AuthorLiu, Xinmin, AuthorLongo, Dan L., AuthorLopez, Oscar L., AuthorLovestone, Simon, AuthorMartinez, Oliver, AuthorMartinot, Jean-Luc, AuthorMattay, Venkata S., AuthorMcDonald, Colm, AuthorMcintosh, Andrew M., AuthorMcMahon, Francis , AuthorMcMahon, Katie L., AuthorMecocci , Patrizia, AuthorMelle, Ingrid, AuthorMeyer-Lindenberg, Andreas, AuthorMohnke, Sebastian, AuthorMontgomery, Grant W.8, AuthorMorris, Derek W., AuthorMosley, Thomas H., AuthorMühleisen, Thomas W., AuthorMüller-Myhsok, Bertram, AuthorNalls, Michael A., AuthorNauck, Matthias, AuthorNichols, Thomas E., AuthorNiessen, Wiro J.3, AuthorNöthen, Markus M., AuthorNyberg, Lars22, AuthorOhi, Kazutaka, AuthorOlvera, Rene L., AuthorOphoff, Roel A.19, AuthorPandolfo, Massimo, AuthorPaus, Tomas, AuthorPausova, Zdenka, AuthorPenninx, Brenda W. J. H., AuthorPike, G. Bruce, AuthorPotkin, Steven G., AuthorPsaty, Bruce M., AuthorReppermund , Simone, AuthorRietschel, Marcella, AuthorRoffman, Joshua L., AuthorRomanczuk-Seiferth, Nina, AuthorRotter, Jerome I., AuthorRyten, Mina, AuthorSacco, Ralph L., AuthorSachdev, Perminder S., AuthorSaykin, Andrew J., AuthorSchmidt, Reinhold6, AuthorSchmidt, Helena, AuthorSchofield, Peter R., AuthorSigursson, Sigurdur, AuthorSimmons, Andrew, AuthorSingleton, Andrew, AuthorSisodiya, Sanjay M., AuthorSmith, Colin, AuthorSmoller, Jordan W., AuthorSoininen, Hilkka, AuthorSteen, Vidar M., AuthorStott, David J., AuthorSussmann, Jessika E., AuthorThalamuthu, Anbupalam, AuthorToga, Arthur W., AuthorTraynor, Bryan J., AuthorTroncoso, Juan, AuthorTsolaki, Magda, AuthorTzourio, Christophe4, AuthorUitterlinden, André G.2, AuthorHernández, Maria C. Valdés26, AuthorVan der Brug, Marcel, AuthorVan der Lugt, Aad3, AuthorVan der Wee, Nic J. A., AuthorVan Haren, Neeltje E. M.19, AuthorVan Tol, Marie-Jose, AuthorVardarajan, Badri N., AuthorVellas, Bruno, AuthorVeltman, Dick J., AuthorVölzke, Henry, AuthorWalter, Henrik, AuthorWardlaw, Joanna M.26, AuthorWassink, Thomas H., AuthorWeale, Michael e. , AuthorWeinberger, Daniel R., AuthorWeiner, Michael, AuthorWen, Wei, AuthorWestman, Eric, AuthorWhite, Tonya3, AuthorWong, Tien Y.14, 15, AuthorWright, Clinton B., AuthorZielke, Ronald H., AuthorZonderman, Alan B., AuthorMartin, Nicholas G.8, AuthorVan Duijn, Cornelia M.2, AuthorWright, Margaret J., AuthorLongstreth, WT W. T. , AuthorSchumann, Gunter18, AuthorGrabe, Hans J., AuthorFranke, Barbara10, 11, 13, AuthorLauner, Lenore J., AuthorMedland, Sarah E.8, AuthorSeshadri, Sudha, AuthorThompson, Paul M.1, AuthorIkram, Arfam2, 3, Author more..
Affiliations:
1Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of University of Southern California, , Los Angeles, California 90292, USA, ou_persistent22              
2Department of Epidemiology, Erasmus University Medical Center, , 3015 CE Rotterdam, The Netherlands, ou_persistent22              
3Department of Radiology and Nuclear Medicine, Erasmus MC, 3015 CE Rotterdam, The Netherlands, ou_persistent22              
4INSERM Unit U1219, University of Bordeaux, 33076 Bordeaux, France, ou_persistent22              
5Department of Genetics & UNC Neuroscience Center, University of North Carolina (UNC),, Chapel Hill, North Carolina, 27599, USA, ou_persistent22              
6Department of Neurology, Clinical Division of Neurogeriatrics, Medical University , Graz, Austria, ou_persistent22              
7Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Graz, Austria, ou_persistent22              
8QIMR Berghofer Medical Research Institute , Brisbane, Queensland 4006, Australia, ou_persistent22              
9Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA, ou_persistent22              
10Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands, ou_persistent22              
11Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands, ou_persistent22              
12Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands, ou_persistent22              
13Donders Institute for Brain, Cognition and Behaviour, External Organizations, ou_55236              
14Academic Medicine Research Institute, Duke-NUS Graduate Medical School, Singapore, Singapore, ou_persistent22              
15Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore, ou_persistent22              
16Memory Aging & Cognition Centre (MACC), National University Health System, Singapore, Singapore, ou_persistent22              
17Department of Pharmacology, National University of Singapore, Singapore, Singapore, ou_persistent22              
18MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, , London, UK, ou_persistent22              
19Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht, The Netherlands, ou_persistent22              
20Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4, ou_persistent22              
21The Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin , Ireland, ou_persistent22              
22Department of Integrative Medical Biology and Umeå Center for Functional Brain Imaging, Umeå Universityander, Umeå, Sweden, ou_persistent22              
23Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois 60616, USA, ou_persistent22              
24Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA, ou_persistent22              
25Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, Illinois 60616, USA, ou_persistent22              
26Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, ou_persistent22              
27Department of Computer Science, Lagos State University, Lagos, P.M.B. 01 LASU, Nigeria, ou_persistent22              
28Language and Genetics Group, MPI for Psycholinguistics, Max Planck Society, ou_55213              

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 Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

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Language(s): eng - English
 Dates: 2017-01-18
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/ncomms13624
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 8 Sequence Number: 13624 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723