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


Adams, HHH and Hibar, DP and Chouraki, V and Stein, JL and Nyquist, PA and Renteria, ME and Trompet, S and Arias-Vasquez, A and Seshadri, S and Desrivieres, S and Beecham, AH and Jahanshad, N and Wittfeld, K and Van der Lee, SJ and Abramovic, L and Alhusaini, S and Amin, N and Andersson, M and Arfanakis, K and Aribisala, BS and Armstrong, NJ and Athanasiu, L and Axelsson, T and Beiser, A and Bernard, M and Bis, JC and Blanken, LME and Blanton, SH and Bohlken, MM and Boks, MP and Bralten, J and Brickman, AM and Carmichael, O and Chakravarty, MM and Chauhan, G and Chen, Q and Ching, CRK and Cuellar-Partida, G and Braber, AD and Doan, NT and Ehrlich, S and Filippi, I and Ge, T and Giddaluru, S and Goldman, AL and Gottesman, RF and Greven, CU and Grimm, O and Griswold, ME and Guadalupe, T and Hass, J and Haukvik, UK and Hilal, S and Hofer, E and Hoehn, D and Holmes, AJ and Hoogman, M and Janowitz, D and Jia, T and Kasperaviciute, D and Kim, S and Klein, M and Kraemer, B and Lee, PH and Liao, J and Liewald, DCM and Lopez, LM and Luciano, M and Macare, C and Marquand, A and Matarin, M and Mather, KA and Mattheisen, M and Mazoyer, B and McKay, DR and McWhirter, R and Milaneschi, Y and Mirza-Schreiber, N and Muetzel, RL and Maniega, SM and Nho, K and Nugent, AC and Loohuis, LMO and Oosterlaan, J and Papmeyer, M and Pappa, I and Pirpamer, L and Pudas, S and Putz, B and Rajan, KB and Ramasamy, A and Richards, JS and Risacher, SL and Roiz-Santianez, R and Rommelse, N and Rose, EJ and Royle, NA and Rundek, T and Samann, PG and Satizabal, CL and Schmaal, L and Schork, AJ and Shen, L and Shin, J and Shumskaya, E and Smith, AV and Sprooten, E and Strike, LT and Teumer, A and Thomson, R and Tordesillas-Gutierrez, D and Toro, R and Trabzuni, D and Vaidya, D and Van der Grond, J and Van der Meer, D and Van Donkelaar, MMJ and Van Eijk, KR and Van Erp, TGM and Van Rooij, D and Walton, E and Westlye, LT and Whelan, CD and Windham, BG and Winkler, AM and Woldehawariat, G and Wolf, C and Wolfers, T and Xu, B and Yanek, LR and Yang, J and Zijdenbos, A and Zwiers, MP and Agartz, I and Aggarwal, NT and Almasy, L and Ames, D and Amouyel, P and Andreassen, OA and Arepalli, S and Assareh, AA and Barral, S and Bastin, ME and Becker, DM and Becker, JT and Bennett, DA and Blangero, J and van Bokhoven, H and Boomsma, DI and Brodaty, H and Brouwer, RM and Brunner, HG and Buckner, RL and Buitelaar, JK and Bulayeva, KB and Cahn, W and Calhoun, VD and Cannon, DM and Cavalleri, GL and Chen, C and Cheng, C-Y and Cichon, S and Cookson, MR and Corvin, A and Crespo-Facorro, B and Curran, JE and Czisch, M and Dale, AM and Davies, GE and De Geus, EJC and De Jager, PL and De Zubicaray, GI and Delanty, N and Depondt, C and DeStefano, AL and Dillman, A and Djurovic, S and Donohoe, G and Drevets, WC and Duggirala, R and Dyer, TD and Erk, S and Espeseth, T and Evans, DA and Fedko, IO and Fernandez, G and Ferrucci, L and Fisher, SE and Fleischman, DA and Ford, I and Foroud, TM and Fox, PT and Francks, C and Fukunaga, M and Gibbs, JR and Glahn, DC and Gollub, RL and Goring, HHH and Grabe, HJ and Green, RC and Gruber, O and Gudnason, V and Guelfi, S and Hansell, NK and Hardy, J and Hartman, CA and Hashimoto, R and Hegenscheid, K and Heinz, A and Le Hellard, S and Hernandez, DG and Heslenfeld, DJ and Ho, B-C and Hoekstra, PJ and Hoffmann, W and Hofman, A and Holsboer, F and Homuth, G and Hosten, N and Hottenga, J-J and Pol, HEH and Ikeda, M and Ikram, MK and Jack Jr, CR and Jenkinson, M and Johnson, R and Jonsson, EG and Jukema, JW and Kahn, RS and Kanai, R and Kloszewska, I and Knopman, DS and Kochunov, P and Kwok, JB and Lawrie, SM and Lemaitre, H and Liu, X and Longo, DL and Longstreth Jr, WT and Lopez, OL and Lovestone, S and Martinez, O and Martinot, J-L and Mattay, VS and McDonald, C and McIntosh, AM and McMahon, KL and McMahon, FJ and Mecocci, P and Melle, I and Meyer-Lindenberg, A and Mohnke, S and Montgomery, GW and Morris, DW and Mosley, TH and Muhleisen, TW and Muller-Myhsok, B and Nalls, MA and Nauck, M and Nichols, TE and Niessen, WJ and Nothen, MM and Nyberg, L and Ohi, K and Olvera, RL and Ophoff, RA and Pandolfo, M and Paus, T and Pausova, Z and Penninx, BWJH and Pike, GB and Potkin, SG and Psaty, BM and Reppermund, S and Rietschel, M and Roffman, JL and Romanczuk-Seiferth, N and Rotter, JI and Ryten, M and Sacco, RL and Sachdev, PS and Saykin, AJ and Schmidt, R and Schofield, PR and Sigurdsson, S and Simmons, A and Singleton, A and Sisodiya, SM and Smith, C and Smoller, JW and Soininen, H and Srikanth, V and Steen, VM and Stott, DJ and Sussmann, JE and Thalamuthu, A and Tiemeier, H and Toga, AW and Traynor, BJ and Troncoso, J and Turner, JA and Tzourio, C and Uitterlinden, AG and Hernandez, MCV and Van der Brug, M and Van der Lugt, A and Van der Wee, NJA and Van Duijn, CM and Van Haren, NEM and Van 't Ent, D and Van Tol, M-J and Vardarajan, BN and Veltman, DJ and Vernooij, MW and Volzke, H and Walter, H and Wardlaw, JM and Wassink, TH and Weale, ME and Weinberger, DR and Weiner, MW and Wen, W and Westman, E and White, T and Wong, TY and Wright, CB and Zielke, HR and Zonderman, AB and Deary, IJ and DeCarli, C and Schmidt, H and Martin, NG and De Craen, AJM and Wright, MJ and Launer, LJ and Schumann, G and Fornage, M and Franke, B and Debette, S and Medland, SE and Ikram, MA and Thompson, PM and the Alzheimerís Disease Neuroimaging Initiative, EPIGEN, IMAGEN, SYS, Novel genetic loci underlying human intracranial volume identified through genome-wide association, Nature Neuroscience, 19, (12) pp. 1569-1582. ISSN 1097-6256 (2016) [Refereed Article]

Copyright Statement

Copyright 2016 Nature America, Inc., part of Springer Nature

DOI: doi:10.1038/nn.4398


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 (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. © 2016 Nature America, Inc., part of Springer Nature. All rights reserved.

Item Details

Item Type:Refereed Article
Keywords:genome wide association, intracranial volume, genetic meta-analysis
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Neurogenetics
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:McWhirter, R (Dr Rebekah McWhirter)
UTAS Author:Srikanth, V (Dr Velandai Srikanth)
ID Code:113772
Year Published:2016
Web of Science® Times Cited:121
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-01-19
Last Modified:2017-11-06

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