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

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Journal Article

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 (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 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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Duke Authors

Cited Authors

  • Adams, HHH; Hibar, DP; Chouraki, V; Stein, JL; Nyquist, PA; Rentería, ME; Trompet, S; Arias-Vasquez, A; Seshadri, S; Desrivières, S; Beecham, AH; Jahanshad, N; Wittfeld, K; Van der Lee, SJ; Abramovic, L; Alhusaini, S; Amin, N; Andersson, M; Arfanakis, K; Aribisala, BS; Armstrong, NJ; Athanasiu, L; Axelsson, T; Beiser, A; Bernard, M; Bis, JC; Blanken, LME; Blanton, SH; Bohlken, MM; Boks, MP; Bralten, J; Brickman, AM; Carmichael, O; Chakravarty, MM; Chauhan, G; Chen, Q; Ching, CRK; Cuellar-Partida, G; Braber, AD; Doan, NT; Ehrlich, S; Filippi, I; Ge, T; Giddaluru, S; Goldman, AL; Gottesman, RF; Greven, CU; Grimm, O; Griswold, ME; Guadalupe, T; Hass, J; Haukvik, UK; Hilal, S; Hofer, E; Hoehn, D; Holmes, AJ; Hoogman, M; Janowitz, D; Jia, T; Kasperaviciute, D; Kim, S; Klein, M; Kraemer, B; Lee, PH; Liao, J; Liewald, DCM; Lopez, LM; Luciano, M; Macare, C; Marquand, A; Matarin, M; Mather, KA; Mattheisen, M; Mazoyer, B; McKay, DR; McWhirter, R; Milaneschi, Y; Mirza-Schreiber, N; Muetzel, RL; Maniega, SM; Nho, K; Nugent, AC; Loohuis, LMO; Oosterlaan, J; Papmeyer, M; Pappa, I; Pirpamer, L; Pudas, S; Pütz, B; Rajan, KB; Ramasamy, A; Richards, JS; Risacher, SL; Roiz-Santiañez, R; Rommelse, N; Rose, EJ; Royle, NA; Rundek, T; Sämann, PG; Satizabal, CL; Schmaal, L; Schork, AJ; Shen, L; Shin, J; Shumskaya, E; Smith, AV; Sprooten, E; Strike, LT; Teumer, A; Thomson, R; Tordesillas-Gutierrez, D; Toro, R; Trabzuni, D; Vaidya, D; Van der Grond, J; 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; Woldehawariat, G; Wolf, C; Wolfers, T; Xu, B; Yanek, LR; Yang, J; Zijdenbos, A; Zwiers, MP; Agartz, I; Aggarwal, NT; 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; Chen, C; Cheng, C-Y; Cichon, S; Cookson, MR; Corvin, A; Crespo-Facorro, B; Curran, JE; Czisch, M; Dale, AM; Davies, GE; De Geus, EJC; De Jager, PL; de Zubicaray, GI; Delanty, N; Depondt, C; DeStefano, AL; Dillman, A; Djurovic, S; Donohoe, G; Drevets, WC; Duggirala, R; Dyer, TD; Erk, S; Espeseth, T; Evans, DA; Fedko, IO; Fernández, G; Ferrucci, L; Fisher, SE; Fleischman, DA; Ford, I; Foroud, TM; Fox, PT; Francks, C; Fukunaga, M; Gibbs, JR; Glahn, DC; Gollub, RL; Göring, HHH; Grabe, HJ; Green, RC; Gruber, O; Gudnason, V; Guelfi, S; 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; Hulshoff Pol, HE; Ikeda, M; Ikram, MK; 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; Longstreth, WT; Lopez, OL; Lovestone, S; Martinez, O; Martinot, J-L; Mattay, VS; McDonald, C; McIntosh, AM; McMahon, KL; McMahon, FJ; 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; Schofield, PR; Sigurdsson, S; Simmons, A; Singleton, A; Sisodiya, SM; Smith, C; Smoller, JW; Soininen, H; Srikanth, V; Steen, VM; Stott, DJ; Sussmann, JE; Thalamuthu, A; Tiemeier, H; Toga, AW; Traynor, BJ; Troncoso, J; Turner, JA; Tzourio, C; Uitterlinden, AG; Hernández, MCV; Van der Brug, M; Van der Lugt, A; Van der Wee, NJA; Van Duijn, CM; Van Haren, NEM; Van T Ent, D; Van Tol, M-J; Vardarajan, BN; Veltman, DJ; Vernooij, MW; 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, HR; Zonderman, AB; Deary, IJ; DeCarli, C; Schmidt, H; Martin, NG; De Craen, AJM; Wright, MJ; Launer, LJ; Schumann, G; Fornage, M; Franke, B; Debette, S; Medland, SE; Ikram, MA; Thompson, PM

Published Date

  • December 2016

Published In

Volume / Issue

  • 19 / 12

Start / End Page

  • 1569 - 1582

PubMed ID

  • 27694991

Pubmed Central ID

  • 27694991

Electronic International Standard Serial Number (EISSN)

  • 1546-1726

International Standard Serial Number (ISSN)

  • 1097-6256

Digital Object Identifier (DOI)

  • 10.1038/nn.4398

Language

  • eng