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

Adams, H. H.H. et al. (2016) Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature Neuroscience, 19(12), pp. 1569-1582. (doi: 10.1038/nn.4398) (PMID:27694991)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott J, Professor David and Ford, Professor Ian
• Authors: Adams, H. H.H., Hibar, D. P., Chouraki, V., Stein, J. L., Nyquist, P. A., Rentería, M. E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivières, S., Beecham, A. H., Jahanshad, N., Wittfeld, K., Van der Lee, S. J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B. S., Armstrong, N. J., Athanasiu, L., Axelsson, T., Beiser, A., Bernard, M., Bis, J. C., Blanken, L. M.E., Blanton, S. H., Bohlken, M. M., Boks, M. P., Bralten, J., Brickman, A. M., Carmichael, O., Chakravarty, M. M., Chauhan, G., Chen, Q., Ching, C. R.K., Cuellar-Partida, G., Braber, A. D., Doan, N. T., Ehrlich, S., Filippi, I., Ge, T., Giddaluru, S., Goldman, A. L., Gottesman, R. F., Greven, C. U., Grimm, O., Griswold, M. E., Guadalupe, T., Hass, J., Haukvik, U. K., Hilal, S., Hofer, E., Hoehn, D., Holmes, A. J., Hoogman, M., Janowitz, D., Jia, T., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P. H., Liao, J., Liewald, D. C.M., Lopez, L. M., Luciano, M., Macare, C., Marquand, A., Matarin, M., Mather, K. A., Mattheisen, M., Mazoyer, B., McKay, D. R., McWhirter, R., Milaneschi, Y., Mirza-Schreiber, N., Muetzel, R. L., Maniega, S. M., Nho, K., Nugent, A. C., Loohuis, L. M. O., Oosterlaan, J., Papmeyer, M., Pappa, I., Pirpamer, L., Pudas, S., Pütz, B., Rajan, K. B., Ramasamy, A., Richards, J. S., Risacher, S. L., Roiz-Santiañez, R., Rommelse, N., Rose, E. J., Royle, N. A., Rundek, T., Sämann, P. G., Satizabal, C. L., Schmaal, L., Schork, A. J., Shen, L., Shin, J., Shumskaya, E., Smith, A. V., Sprooten, E., Strike, L. T., Teumer, A., Thomson, R., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Vaidya, D., Van der Grond, J., Van der Meer, D., Van Donkelaar, M. M.J., Van Eijk, K. R., Van Erp, T. G.M., Van Rooij, D., Walton, E., Westlye, L. T., Whelan, C. D., Windham, B. G., Winkler, A. M., Woldehawariat, G., Wolf, C., Wolfers, T., Xu, B., Yanek, L. R., Yang, J., Zijdenbos, A., Zwiers, M. P., Agartz, I., Aggarwal, N. T., Almasy, L., Ames, D., Amouyel, P., Andreassen, O. A., Arepalli, S., Assareh, A. A., Barral, S., Bastin, M. E., Becker, D. M., Becker, J. T., Bennett, D. A., Blangero, J., van Bokhoven, H., Boomsma, D. I., Brodaty, H., Brouwer, R. M., Brunner, H. G., Buckner, R. L., Buitelaar, J. K., Bulayeva, K. B., Cahn, W., Calhoun, V. D., Cannon, D. M., Cavalleri, G. L., Chen, C., Cheng, C.-Y., Cichon, S., Cookson, M. R., Corvin, A., Crespo-Facorro, B., Curran, J. E., Czisch, M., Dale, A. M., Davies, G. E., De Geus, E. J.C., De Jager, P. L., de Zubicaray, G. I., Delanty, N., Depondt, C., DeStefano, A. L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W. C., Duggirala, R., Dyer, T. D., Erk, S., Espeseth, T., Evans, D. A., Fedko, I. O., Fernández, G., Ferrucci, L., Fisher, S. E., Fleischman, D. A., Ford, I., Foroud, T. M., Fox, P. T., Francks, C., Fukunaga, M., Gibbs, J. R., Glahn, D. C., Gollub, R. L., Göring, H. H.H., Grabe, H. J., Green, R. C., Gruber, O., Gudnason, V., Guelfi, S., Hansell, N. K., Hardy, J., Hartman, C. A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D. G., Heslenfeld, D. J., Ho, B.-C., Hoekstra, P. J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J.-J., Pol, H. E. H., Ikeda, M., Ikram, M. K., Jack Jr, C. R., Jenkinson, M., Johnson, R., Jönsson, E. G., Jukema, J. W., Kahn, R. S., Kanai, R., Kloszewska, I., Knopman, D. S., Kochunov, P., Kwok, J. B., Lawrie, S. M., Lemaître, H., Liu, X., Longo, D. L., Longstreth Jr, W.T., Lopez, O. L., Lovestone, S., Martinez, O., Martinot, J.-L., Mattay, V. S., McDonald, C., McIntosh, A. M., McMahon, K. L., McMahon, F. J., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G. W., Morris, D. W., Mosley, T. H., Mühleisen, T. W., Müller-Myhsok, B., Nalls, M. A., Nauck, M., Nichols, T. E., Niessen, W. J., Nöthen, M. M., Nyberg, L., Ohi, K., Olvera, R. L., Ophoff, R. A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B. W.J.H., Pike, G. B., Potkin, S. G., Psaty, B. M., Reppermund, S., Rietschel, M., Roffman, J. L., Romanczuk-Seiferth, N., Rotter, J. I., Ryten, M., Sacco, R. L., Sachdev, P. S., Saykin, A. J., Schmidt, R., Schofield, P. R., Sigurdsson, S., Simmons, A., Singleton, A., Sisodiya, S. M., Smith, C., Smoller, J. W., Soininen, H., Srikanth, V., Steen, V. M., Stott, D. J., Sussmann, J. E., Thalamuthu, A., Tiemeier, H., Toga, A. W., Traynor, B. J., Troncoso, J., Turner, J. A., Tzourio, C., Uitterlinden, A. G., Hernández, M. C. V., Van der Brug, M., Van der Lugt, A., Van der Wee, N. J.A., Van Duijn, C. M., Van Haren, N. E.M., Van T Ent, D., Van Tol, M.-J., Vardarajan, B. N., Veltman, D. J., Vernooij, M. W., Völzke, H., Walter, H., Wardlaw, J. M., Wassink, T. H., Weale, M. E., Weinberger, D. R., Weiner, M. W., Wen, W., Westman, E., White, T., Wong, T. Y., Wright, C. B., Zielke, H. R., Zonderman, A. B., Deary, I. J., DeCarli, C., Schmidt, H., Martin, N. G., De Craen, A. J.M., Wright, M. J., Launer, L. J., Schumann, G., Fornage, M., Franke, B., Debette, S., Medland, S. E., Ikram, M. A., and Thompson, P. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Nature Neuroscience
• Publisher: Nature Publishing Group
• ISSN: 1097-6256
• ISSN (Online): 1546-1726
• Published Online: 03 October 2016
• Copyright Holders: Copyright © 2016 Nature America, Inc.
• First Published: First published in Nature Neuroscience 19(12): 1569-1582
• Publisher Policy: Reproduced in accordance with the publisher copyright policy