Novel genetic loci associated with hippocampal volume

van der Wee, Nj; van't Ent, Dennis; Stein, Jl L.; Adams, Hieab H. Hh; Jahanshad, Neda; Chauhan, Ganesh; Renteria, Me E. (Miguel); Vernooij, Mw W. (Meike); Hofer, Edith; Jørgensen, Kn N. (Kjetil N.); Jorgensen, Kjetil N.; Ikram, M. Kamran; Arias-Vasquez, Alejandro; Kamran Ikram, M.; Desrivières, Sylvane; Lee, Ph H. (Phil); Liewald, Dc C. (David C.); Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Lopez, Lm M. (Lorna); Andersson, Micael; Arfanakis, Konstantinos A.; Marquand, Af F. (Andre F.); Mather, R.; Mather, Ka; Athanasiu, Lavinia; Axelsson, Tomas; McKay, Dr R. (David R.); Beiser, Alexa; Muñoz Maniega, Susanna; Bernard, Manon; Bohlken, Marc Mm; Nugent, Ac C. (Allison); Boks, Marco P. M. (Marco); Bralten, Janita; Loohuis, Lm M. O. (Loes M. Olde); Carmichael, Owen; Mallar Chakravarty, M.; Chakravarty, Mm Mallar; Chen, Qiang; Richards, Js S. (Jennifer S.); Chouraki, Vincent; Puetz, Benno; Cuellar-Partida, Gabriel; den Braber, A.; Crivello, Fabrice; Den Braber, Anouk; Risacher, Sl L. (Shannon); Ehrlich, Stefan M. (Stefan); Rose, Ej J. (Emma); Giddaluru, Sudheer; Royle, Na A. (Natalie); Sämann, Pg G. (Philipp); Grimm, Oliver; Griswold, Michael E.; Samann, Philipp G.; Guadalupe, Tulio; Gutman, Boris A. (Boris A.); Hass, Johanna; Satizabal, Cl L. (Claudia L.); Maniega, Susana Munoz; Hoehn, David; Saemann, Philipp G.; Hoogman, Martine; Schork, N. J. (Nicholas); Janowitz, Deborah; Jia, Tianye; Schork, Aj; Karbalai, Nazanin; Olde Loohuis, Loes M.; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Sprooten, R. (Roy); Smith, Av V. (Albert Vernon); Liewald, David C. M.; Strike, V. M. (Vanessa); Luciano, Michelle; Strike, Lt; Macare, Christine; Ho, Avram J.; Matarin, Mar; van der Grond, J. (Jeroen); van der Lee, S. (Sven); Mattheisen, Manuel; Van Der Lee, Sven J.; Milaneschi, Yuri; Van der Lee, Sj; Van Donkelaar, Mm; Nho, Kwangsik; Van Eijk, Kr; Nyquist, Paul; Van Erp, Tg; Westlye, Lt T. (Lars); Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Whelan, Cd D. (Christopher); Ramasamy, Adaikalavan; Windham, Bg G. (B Gwen); Roiz-Santiañez, Roberto; Winkler, Am M. (Anderson); Yanek, Lr R. (Lisa); Rommelse, Nanda; Ropele, Stefan; Zubicaray, G. I. (Greig) de; Pol, Hilleke E. Hulshoff; Rundek, Tatjana; Pol, He H.; Saremi, Arvin; Jenkinson, S. (Sarah); Schmaal, Lianne; Joensson, Erik G.; Jönsson, Eg G. (Erik G.); Shen, Li; Shin, Jean; Shumskaya, Elena; Kahn, Rs; Sprooten, Emma; Knopman, Ds S. (David S.); Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Kwok, Jb B. (John B.); Lawrie, Sm; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Longo, Dl L. (Dan L.); Lopez, Ol L. (Oscar L.); Martinot, Jl-L. (Jean-Luc); Van der Meer, Dennis; Van Donkelaar, Marjolein M. J. (Marjolein M. J.); Mattay, Vs S. (Venkata S.); Van Rooij, Daan; McIntosh, Am M. (Andrew); McMahon, Fj J. (Francis J.); Walton, Esther; McMahon, Kl L. (Katie L.); Montgomery, Gw W. (Grant W.); Morris, Dw W. (Derek W); Wittfeld, Katharina; Mosley, Th H. (Thomas H.); Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Mühleisen, Tw W. (Thomas); Mueller-Myhsok, Bertram; Yang, Jingyun; Zijdenbos, Alex P.; Zwiers, Marcel P. (Marcel); Agartz, Ingrid; Nichols, Te E. (Thomas); Almasy, Laura; Ames, David; Amouyel, Philippe; Niessen, Wj J. (Wiro); Nothen, Markus M.; Arepalli, Sampath; Assareh, Amelia Aa; Barral, Sandra; Olvera, Rl L. (Rene); Ophoff, Ra A. (Roel); Penninx, Bw W. J. H. (Brenda); Potkin, Sg G. (Steven); Psaty, Bm M. (Bruce); Blangero, John; Roffman, Jl L. (Joshua); van Bokhoven, Hans; Seiferth, N. (Nina); Brodaty, Henry; Rotter, Ji I. (Jerome I.); Buckner, Randy L.; Sacco, Rl L. (Ralph L.); S. Sachdev, Perminder; Sachdev, Ps S. (Perminder); Saykin, Aj J. (Andrew); Schofield, C. J. (Christopher); Cahn, Wiepke; Schofield, Pr; Schofield, Peter R.; Simmons, Andy; van 't Ent, Dennis; Sisodiya, Sm M. (Sanjay); Cichon, Sven; Smoller, Jw W.; Corvin, Aiden; Steen, Vm M. (Vidar); Crespo-Facorro, Benedicto; Stott, Dj J. (David J.); Czisch, Michael; Sussmann, Je; Toga, Aw W. (Arthur W.); Traynor, Bj; Ejc, de Geus; Uitterlinden, Ag G. (André); Lugt, A. (Aad) van der; Wee, N. J. (Nic) van der; de Craen, Anton J. M.; Van Der Wee, Nic J. A.; Debette, Stéphanie; DeCarli, Charles; de Geus, Eco J. C.; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L. (Anita); Donohoe, Gary; Dillman, Allissa; Van Haren, Ne; Djurovic, Srdjan; Drevets, Wayne C.; Dyer, Thomas D.; Duggirala, Ravi; Tol, M. J. D. (Marie-José) van; Enzinger, Christian; Erk, Susanne; Van’t Ent, Dennis; Espeseth, Thomas; Van Tol, Mj; Fernández, Guillén; Ferrucci, Luigi U. V. M.; Vardarajan, Bn N. (Badri); Muhleisen, Thomas W.; Voelzke, Henry; Ford, Ian; Fornage, Myriam; Muller-Myhsok, Bertram; Veltman, Dj J. (Dick); Wassink, Thomas H.; Francks, Clyde; Fukunaga, Masaki; Raphael Gibbs, J.; Gibbs, J. Raphael; Wassink, A. M. J. (Annemarie); Wardlaw, Jm; Dyer, Thomas; Göring, Harald H. Hh; Wassink, Th; Weale, Me E. (Michael); Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Weinberger, Dr R. (Daniel R.); Weiner, Mw W. (Michael W.); Wong, Ty Y. (Tien Y.); Hardy, John; Wright, Cb B. (Clinton B.); Hashimoto, Ryota; Hegenscheid, Katrin; Zielke, Rh H. (Ronald H.); Heinz, Andreas; Hellard, Stephanie Le; Le Hellard, Stephanie; Martin, Ng G. (Nicholas); Ho, Beng-Choon; Van Duijn, Cm; Wright, Mj J. (Margaret); Launer, Lj J. (Lenore); Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Medland, Se E. (Sarah Elizabeth); Homuth, Georg; Hosten, Norbert; Hibar, Dp P. (Derrek); Huentelman, Matthew J. (Matthew); Thompson, Pm; Hieab, H. H. Adams; Hulshoff Pol, Hilleke E.; Ikeda, Masashi; Ikram, M. K. (M Kamran); Jenkinson, Mark; Johnson, Robert; Wouter Jukema, J.; Bis, Jc C. (Joshua); Armstrong, Nj J. (Nicola J.); Jukema, Jw Wouter; Kanai, Ryota; Aribisala, Bs; Kloszewska, Iwona; Beecham, Ah H. (Ashley); Kochunov, Peter; Valdés-Hernandez, Maria C.; Blanton, Sh H. (Susan H.); Bralten, L. B. C. (Linda); Lemaître, Hervé; Liu, Xinmin; Brickman, Am M. (Adam M.); Ching, Cr R. K. (Christopher); Lovestone, Simon; Martinez, Oliver; Braber, A. (Anouk) den; Doan, Nt T. (Nhat Trung); McDonald, Colm; Goldman, Al L. (Aaron L.); Gottesman, Rf F. (Rebecca); Griswold, Me D. (Michael); Haukvik, Uk K. (Unn); Mecocci, Patrizia; Höhn, David; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Holmes, Aj J. (Avram); Eijk, K. R. (Kristel) van; Mcintosh, Andrew; Erp, T. G. M. (Theo G.) van; Mcmahon, Katie L.; Müller-Myhsok, Bertram; Nalls, Michael A. (Michael); Björnsson, A. (Asgeir); Nauck, Matthias; Andreassen, Oa A. (Ole A.); Bastin, Me E. (Mark); Nöthen, Markus Mm; Becker, Dm M. (Diane M.); Nyberg, Lars; Ohi, Kazutaka; Becker, Jt T.; Bennett, Da A. (David A.); Bokhoven, H. (Hans) van; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Boomsma, Di I. (Dorret); Bruce Pike, G.; Pike, Gb Bruce; Brouwer, Rm M. (Rachel); Brunner, Hg G.; Buckner, M.; Reppermund, Simone; Rietschel, Marcella; Buckner, Rl; Buitelaar, Jk K. (Jan); Romanczuk-Seiferth, Nina; Bulayeva, Kb; Ryten, Mina; Calhoun, Vd; Cannon, Dm M. (Dara); Cavalleri, Gl; Cheng, Cy-Y. (Ching-Yu); Schmidt, Reinhold E.; Schmidt, Helena; Cookson, Mr R. (Mark); Curran, Je E. (Joanne); Sigursson, Sigurdur; Dale, Am M. (Anders); Singleton, Andrew; Davies, Ge E. (Gareth); De Craen, Aj; Smith, Colin; Craen, A. J. (Anton) de; Soininen, Hilkka; De Geus, Ej; Geus, E. J. C. (Eco) de; De Jager, Pl; Jager, P. L. (Philip) de; Thalamuthu, Anbupalam; De Zubicaray, Gi; Deary, Ij J. (Ian J.); Ikram, Kamran; Troncoso, Juan C. (Juan); Tsolaki, Magda; Tzourio, Christophe; Ikram, Mk Arfan; Donohoe, D. J. (Dennis); Drevets, D. A. (Douglas); Van der Brug, Marcel; van der Lugt, Aad; Drevets, Wc; Dyer, M. D. (Matthew); Dyer, Td; Fedko, Io O. (Iryna O.); Fisher, Se E. (Simon); Fleischman, Da; Foroud, Tm; Vellas, Bruno; Fox, Pt T. (Peter); Völzke, Henry; Walter, Henrik J. (Henrik); Glahn, Dc C. (David); Goring, Harald H. H.; Gollub, Rl L. (Randy); Green, Rc C. (Robert C.); Haberg, Asta K.; Håberg, Ak K. (Asta K.); Hansell, Nk K. (Narelle); Wen, Wei; Westman, Eric; White, Tonya J. H. (Tonya); Hartman, Ca A. (C.); Heinz, J. (Judith); Hernandez, Dg G. (Dena); Heslenfeld, Dj J. (Dirk); Zonderman, Alan B.; Ho, Bc-C. (Beng-Choon); Hoekstra, Pj J. (Pieter); van Duijn, Cornelia M.; Hottenga, Jj J. (Jouke Jan); Longstreth, Jr. Wt T.; Jack, Cr R. (Clifford R.); Schumann, Gunter; Hernández, Mc C. V. (Maria C. Valdés); Brug, M. P. (Marcel) van der; Franke, Barbara; Haren, N. E. M. (Neeltje E.) van; Ent, D. (Dennis) van 't; Seshadri, Sudha; Duijn, C. M. (Cock) van; Grabe, Hj J. (Hans Jörgen); Arfan Ikram, M.; Ikram, M. Arfan

Published in

Nature Research, Nature Communications, 1(8), 2017

DOI: 10.1038/ncomms13624

Tools

Export citation

Search in Google Scholar

Novel genetic loci associated with hippocampal volume

Journal article published in 2017 by Nj van der Wee, Dennis van't Ent, Jl L. Stein, Hieab H. Hh Adams, Neda Jahanshad, Ganesh Chauhan, Me E. (Miguel) Renteria, Mw W. (Meike) Vernooij, Edith Hofer, Kn N. (Kjetil N.) Jørgensen, Kjetil N. Jorgensen, M. Kamran Ikram, Alejandro Arias-Vasquez, M. Kamran Ikram, Sylvane Desrivières and other authors.

This paper is made freely available by the publisher.

Full text: Download

Preprint: archiving allowed

Upload

Postprint: archiving forbidden

Published version: archiving allowed

Upload

Policy details

Data provided by

Abstract

AbstractThe 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 (r_g=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Published in

Links

Tools

Novel genetic loci associated with hippocampal volume

Abstract