Novel genetic loci associated with hippocampal volume.

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Journal Article

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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Duke Authors

Cited Authors

  • Hibar, DP; Adams, HHH; Jahanshad, N; Chauhan, G; Stein, JL; Hofer, E; Renteria, ME; Bis, JC; Arias-Vasquez, A; Ikram, MK; Desrivières, S; Vernooij, MW; Abramovic, L; Alhusaini, S; Amin, N; Andersson, M; Arfanakis, K; Aribisala, BS; Armstrong, NJ; Athanasiu, L; Axelsson, T; Beecham, AH; Beiser, A; Bernard, M; Blanton, SH; Bohlken, MM; Boks, MP; Bralten, J; Brickman, AM; Carmichael, O; Chakravarty, MM; Chen, Q; Ching, CRK; Chouraki, V; Cuellar-Partida, G; Crivello, F; Den Braber, A; Doan, NT; Ehrlich, S; Giddaluru, S; Goldman, AL; Gottesman, RF; Grimm, O; Griswold, ME; Guadalupe, T; Gutman, BA; Hass, J; Haukvik, UK; Hoehn, D; Holmes, AJ; Hoogman, M; Janowitz, D; Jia, T; Jørgensen, KN; Karbalai, N; Kasperaviciute, D; Kim, S; Klein, M; Kraemer, B; Lee, PH; Liewald, DCM; Lopez, LM; Luciano, M; Macare, C; Marquand, AF; Matarin, M; Mather, KA; Mattheisen, M; McKay, DR; Milaneschi, Y; Muñoz Maniega, S; Nho, K; Nugent, AC; Nyquist, P; Loohuis, LMO; Oosterlaan, J; Papmeyer, M; Pirpamer, L; Pütz, B; Ramasamy, A; Richards, JS; Risacher, SL; Roiz-Santiañez, R; Rommelse, N; Ropele, S; Rose, EJ; Royle, NA; Rundek, T; Sämann, PG; Saremi, A; Satizabal, CL; Schmaal, L; Schork, AJ; Shen, L; Shin, J; Shumskaya, E; Smith, AV; Sprooten, E; Strike, LT; Teumer, A; Tordesillas-Gutierrez, D; Toro, R; Trabzuni, D; Trompet, S; Vaidya, D; Van der Grond, J; Van der Lee, SJ; Van der Meer, D; Van Donkelaar, MMJ; Van Eijk, KR; Van Erp, TGM; Van Rooij, D; Walton, E; Westlye, LT; Whelan, CD; Windham, BG; Winkler, AM; Wittfeld, K; Woldehawariat, G; Wolf, C; Wolfers, T; Yanek, LR; Yang, J; Zijdenbos, A; Zwiers, MP; Agartz, I; Almasy, L; Ames, D; Amouyel, P; Andreassen, OA; Arepalli, S; Assareh, AA; Barral, S; Bastin, ME; Becker, DM; Becker, JT; Bennett, DA; Blangero, J; van Bokhoven, H; Boomsma, DI; Brodaty, H; Brouwer, RM; Brunner, HG; Buckner, RL; Buitelaar, JK; Bulayeva, KB; Cahn, W; Calhoun, VD; Cannon, DM; Cavalleri, GL; Cheng, C-Y; Cichon, S; Cookson, MR; Corvin, A; Crespo-Facorro, B; Curran, JE; Czisch, M; Dale, AM; Davies, GE; De Craen, AJM; De Geus, EJC; De Jager, PL; De Zubicaray, GI; Deary, IJ; Debette, S; DeCarli, C; Delanty, N; Depondt, C; DeStefano, A; Dillman, A; Djurovic, S; Donohoe, G; Drevets, WC; Duggirala, R; Dyer, TD; Enzinger, C; Erk, S; Espeseth, T; Fedko, IO; Fernández, G; Ferrucci, L; Fisher, SE; Fleischman, DA; Ford, I; Fornage, M; Foroud, TM; Fox, PT; Francks, C; Fukunaga, M; Gibbs, JR; Glahn, DC; Gollub, RL; Göring, HHH; Green, RC; Gruber, O; Gudnason, V; Guelfi, S; Håberg, AK; Hansell, NK; Hardy, J; Hartman, CA; Hashimoto, R; Hegenscheid, K; Heinz, A; Le Hellard, S; Hernandez, DG; Heslenfeld, DJ; Ho, B-C; Hoekstra, PJ; Hoffmann, W; Hofman, A; Holsboer, F; Homuth, G; Hosten, N; Hottenga, J-J; Huentelman, M; Hulshoff Pol, HE; Ikeda, M; Jack, CR; Jenkinson, M; Johnson, R; Jönsson, EG; Jukema, JW; Kahn, RS; Kanai, R; Kloszewska, I; Knopman, DS; Kochunov, P; Kwok, JB; Lawrie, SM; Lemaître, H; Liu, X; Longo, DL; Lopez, OL; Lovestone, S; Martinez, O; Martinot, J-L; Mattay, VS; McDonald, C; McIntosh, AM; McMahon, FJ; McMahon, KL; Mecocci, P; Melle, I; Meyer-Lindenberg, A; Mohnke, S; Montgomery, GW; Morris, DW; Mosley, TH; Mühleisen, TW; Müller-Myhsok, B; Nalls, MA; Nauck, M; Nichols, TE; Niessen, WJ; Nöthen, MM; Nyberg, L; Ohi, K; Olvera, RL; Ophoff, RA; Pandolfo, M; Paus, T; Pausova, Z; Penninx, BWJH; Pike, GB; Potkin, SG; Psaty, BM; Reppermund, S; Rietschel, M; Roffman, JL; Romanczuk-Seiferth, N; Rotter, JI; Ryten, M; Sacco, RL; Sachdev, PS; Saykin, AJ; Schmidt, R; Schmidt, H; Schofield, PR; Sigursson, S; Simmons, A; Singleton, A; Sisodiya, SM; Smith, C; Smoller, JW; Soininen, H; Steen, VM; Stott, DJ; Sussmann, JE; Thalamuthu, A; Toga, AW; Traynor, BJ; Troncoso, J; Tsolaki, M; Tzourio, C; Uitterlinden, AG; Hernández, MCV; Van der Brug, M; van der Lugt, A; van der Wee, NJA; Van Haren, NEM; van 't Ent, D; Van Tol, M-J; Vardarajan, BN; Vellas, B; Veltman, DJ; Völzke, H; Walter, H; Wardlaw, JM; Wassink, TH; Weale, ME; Weinberger, DR; Weiner, MW; Wen, W; Westman, E; White, T; Wong, TY; Wright, CB; Zielke, RH; Zonderman, AB; Martin, NG; Van Duijn, CM; Wright, MJ; Longstreth, WT; Schumann, G; Grabe, HJ; Franke, B; Launer, LJ; Medland, SE; Seshadri, S; Thompson, PM; Ikram, MA

Published Date

  • January 18, 2017

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 13624 -

PubMed ID

  • 28098162

Pubmed Central ID

  • 28098162

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms13624

Language

  • eng

Conference Location

  • England