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Novel genetic loci underlying human intracranial volume identified through genome-wide association
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4377181
Author(s)
Adams, H. H.; Hibar, D. P.; Chouraki, V.; Stein, J. L.; Nyquist, P. A.; Renteria, M. E.; Trompet, S.; Arias-Vasquez, A.; Seshadri, S.; Desrivieres, 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.; 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.; 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.; 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.; Oosterlaan, J.; Papmeyer, M.; Pappa, I.; Pirpamer, L.; Pudas, S.; Putz, B.; Rajan, K. B.; Ramasamy, A.; Richards, J. S.; Risacher, S. L.; Roiz-Santianez, R.; Rommelse, N.; Rose, E. J.; Royle, N. A.; Rundek, T.; Samann, 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.; Van Eijk, K. R.; Van Erp, T. G.; 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.; 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.; Fernandez, 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.; Goring, 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.; Ikeda, M.; Ikram, M. K.; Jack, C. R.; Jr.,; Jenkinson, M.; Johnson, R.; Jonsson, E. G.; Jukema, J. W.; Kahn, R. S.; Kanai, R.; Kloszewska, I.; Knopman, D. S.; Kochunov, P.; Kwok, J. B.; Lawrie, S. M.; Lemaitre, H.; Liu, X.; Longo, D. L.; Longstreth, W. T.; Jr.,; 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.; Muhleisen, T. W.; Muller-Myhsok, B.; Nalls, M. A.; Nauck, M.; Nichols, T. E.; Niessen, W. J.; Nothen, M. M.; Nyberg, L.; Ohi, K.; Olvera, R. L.; Ophoff, R. A.; Pandolfo, M.; Paus, T.; Pausova, Z.; Penninx, B. W.; 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.; Hernandez, M. C.; Van der Brug, M.; Van der Lugt, A.; Van der Wee, N. J.; Van Duijn, C. M.; Van Haren, N. E.; Van, T. Ent D.; Van Tol, M. J.; Vardarajan, B. N.; Veltman, D. J.; Vernooij, M. W.; Volzke, 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.; Wright, M. J.; Launer, L. J.; Schumann, G.; Fornage, M.; Franke, B.; Debette, S.; Medland, S. E.; Ikram, M. A.; Thompson, P. M.
Novel genetic loci underlying human intracranial volume identified through genome-wide association
Journal
Nature Neuroscience
Volume
19
Number
12
Pages / Article-Number
1569-1582
Mesh terms
Brain, pathology; Cognition, physiology; European Continental Ancestry Group; Genetic Loci, genetics; Genetic Predisposition to Disease; Genome-Wide Association Study, methods; Humans; Oncogene Protein v-akt, genetics; Parkinson Disease, genetics; Phenotype; Phosphatidylinositol 3-Kinases, genetics; Polymorphism, Single Nucleotide, genetics
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 (rhogenetic = 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.
