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Genetic variants for head size share genes and pathways with cancer.
Knol, M. J. ; Poot, R. A. ; Evans, T. E. ; Satizabal, C. L. ; Mishra, A. ; Sargurupremraj, M. ; van der Auwera, S.DZNE* ; Duperron, M.-G. ; Jian, X. ; Hostettler, I. C. ; van Dam-Nolen, D. H. K. ; Lamballais, S. ; Pawlak, M. A. ; Lewis, C. E. ; Carrion-Castillo, A. ; van Erp, T. G. M. ; Reinbold, C. S. ; Shin, J. ; Scholz, M.Extern* ; Håberg, A. K. ; Kämpe, A. ; Li, G. H. Y. ; Avinun, R. ; Atkins, J. R. ; Hsu, F.-C. ; Amod, A. R. ; Lam, M. ; Tsuchida, A. ; Teunissen, M. W. A. ; Aygün, N. ; Patel, Y. ; Liang, D. ; Beiser, A. S. ; Beyer, F. ; Bis, J. C. ; Bos, D. ; Bryan, R. N. ; Bülow, R. ; Caspers, S. ; Catheline, G. ; Cecil, C. A. M. ; Dalvie, S. ; Dartigues, J.-F. ; DeCarli, C. ; Enlund-Cerullo, M. ; Ford, J. M. ; Franke, B. ; Freedman, B. I. ; Friedrich, N. ; Green, M. J. ; Haworth, S. ; Helmer, C. ; Hoffmann, P. ; Homuth, G. ; Ikram, M. K. ; Jack, C. R. ; Jahanshad, N. ; Jockwitz, C. ; Kamatani, Y. ; Knodt, A. R. ; Li, S. ; Lim, K. ; Longstreth, W. T. ; Macciardi, F. ; Heart, C. f. ; Epidemiology, A. R. i. G. (Collaboration Author) ; Meta-Analysis, E. N. G. t. (Collaboration Author) ; Mäkitie, O. ; Mazoyer, B. ; Medland, S. E. ; Miyamoto, S. ; Moebus, S. ; Mosley, T. H. ; Muetzel, R. ; Mühleisen, T. W. ; Nagata, M. ; Nakahara, S. ; Palmer, N. D. ; Pausova, Z. ; Preda, A. ; Quidé, Y. ; Reay, W. R. ; Roshchupkin, G. V. ; Schmidt, R. ; Schreiner, P. J. ; Setoh, K. ; Shapland, C. Y. ; Sidney, S. ; St Pourcain, B. ; Stein, J. L. ; Tabara, Y. ; Teumer, A. ; Uhlmann, A. ; van der Lugt, A. ; Vernooij, M. W. ; Werring, D. J. ; Windham, B. G. ; Witte, A. V. ; Wittfeld, K.DZNE* ; Yang, Q. ; Yoshida, K. ; Brunner, H. G. ; Le Grand, Q.Extern* ; Sim, K. ; Stein, D. J. ; Bowden, D. W. ; Cairns, M. J. ; Hariri, A. R. ; Cheung, C.-L. ; Andersson, S. ; Villringer, A. ; Paus, T. ; Cichon, S. ; Calhoun, V. D. ; Crivello, F. ; Launer, L. J. ; White, T. ; Koudstaal, P. J. ; Houlden, H. ; Fornage, M. ; Matsuda, F. ; Grabe, H.Extern* ; Ikram, M. A. ; Debette, S. ; Thompson, P. M. ; Seshadri, S. ; Adams, H. H. H. ; Amouyel, P. (Contributor) ; Arfanakis, K. (Contributor) ; Aribisala, B. S. (Contributor) ; Bastin, M. E. (Contributor) ; Chauhan, G. (Contributor) ; Chen, C. (Contributor) ; Cheng, C.-Y. (Contributor) ; de Jager, P. L. (Contributor) ; Deary, I. J. (Contributor) ; Fleischman, D. A. (Contributor) ; Gottesman, R. F. (Contributor) ; Gudnason, V. (Contributor) ; Hilal, S. (Contributor) ; Hofer, E. (Contributor) ; Janowitz, D. (Contributor) ; Jukema, J. W. (Contributor) ; Liewald, D. C. M. (Contributor) ; Lopez, L. M. (Contributor) ; Lopez, O. (Contributor) ; Luciano, M. (Contributor) ; Martinez, O. (Contributor) ; Niessen, W. J. (Contributor) ; Nyquist, P. (Contributor) ; Rotter, J. I. (Contributor) ; Rundek, T. (Contributor) ; Sacco, R. L. (Contributor) ; Schmidt, H. (Contributor) ; Tiemeier, H. (Contributor) ; Trompet, S. (Contributor) ; van der Grond, J. (Contributor) ; Völzke, H. (Contributor) ; Wardlaw, J. M. (Contributor) ; Yanek, L. (Contributor) ; Yang, J. (Contributor) ; Agartz, I. (Contributor) ; Alhusaini, S. (Contributor) ; Almasy, L. (Contributor) ; Ames, D. (Contributor) ; Amunts, K. (Contributor) ; Andreassen, O. A. (Contributor) ; Armstrong, N. (Contributor) ; Bernard, M. (Contributor) ; Blangero, J. (Contributor) ; Blanken, L. M. E. (Contributor) ; Boks, M. P. (Contributor) ; Boomsma, D. I. (Contributor) ; Brickman, A. M. (Contributor) ; Brodaty, H. (Contributor) ; Buckner, R. L. (Contributor) ; Buitelaar, J. K. (Contributor) ; Cannon, D. M. (Contributor) ; Carr, V. J. (Contributor) ; Catts, S. V. (Contributor) ; Chakravarty, M. M. (Contributor) ; Chen, Q. (Contributor) ; Ching, C. R. K. (Contributor) ; Corvin, A. (Contributor) ; Crespo-Facorro, B. (Contributor) ; Curran, J. E. (Contributor) ; Davies, G. E. (Contributor) ; de Geus, E. J. C. (Contributor) ; de Zubicaray, G. I. (Contributor) ; den Braber, A. (Contributor) ; Desrivières, S. (Contributor) ; Dillman, A. (Contributor) ; Djurovic, S. (Contributor) ; Drevets, W. C. (Contributor) ; Duggirala, R. (Contributor) ; Ehrlich, S. (Contributor) ; Erk, S. (Contributor) ; Espeseth, T. (Contributor) ; Fedko, I. O. (Contributor) ; Fernández, G. (Contributor) ; Fisher, S. E. (Contributor) ; Foroud, T. M. (Contributor) ; Ge, T. (Contributor) ; Giddaluru, S. (Contributor) ; Glahn, D. C. (Contributor) ; Goldman, A. L. (Contributor) ; Green, R. C. (Contributor) ; Greven, C. U. (Contributor) ; Grimm, O. (Contributor) ; Hansell, N. K. (Contributor) ; Hartman, C. A. (Contributor) ; Hashimoto, R. (Contributor) ; Heinz, A. (Contributor) ; Henskens, F. (Contributor) ; Hibar, D. P. (Contributor) ; Ho, B.-C. (Contributor) ; Hoekstra, P. J. (Contributor) ; Holmes, A. J. (Contributor) ; Hoogman, M. (Contributor) ; Hottenga, J.-J. (Contributor) ; Hulshoff Pol, H. E. (Contributor) ; Jablensky, A. (Contributor) ; Jenkinson, M. (Contributor) ; Jia, T. (Contributor) ; Jöckel, K.-H. (Contributor) ; Jönsson, E. G. (Contributor) ; Kim, S. (Contributor) ; Klein, M. (Contributor) ; Kochunov, P. (Contributor) ; Kwok, J. B. (Contributor) ; Lawrie, S. M. (Contributor) ; Le Hellard, S. (Contributor) ; Lemaître, H. (Contributor) ; Loughland, C. (Contributor) ; Marquand, A. F. (Contributor) ; Martin, N. G. (Contributor) ; Martinot, J.-L. (Contributor) ; Matarin, M. (Contributor) ; Mathalon, D. H. (Contributor) ; Mather, K. A. (Contributor) ; Mattay, V. S. (Contributor) ; McDonald, C. (Contributor) ; McMahon, F. J. (Contributor) ; McMahon, K. L. (Contributor) ; E, R. (Contributor) ; McWhirter (Contributor) ; Mecocci, P. (Contributor) ; Melle, I. (Contributor) ; Meyer-Lindenberg, A. (Contributor) ; Michie, P. T. (Contributor) ; Milaneschi, Y. (Contributor) ; Morris, D. W. (Contributor) ; Mowry, B. (Contributor) ; Nho, K. (Contributor) ; Nichols, T. E. (Contributor) ; Nöthen, M. N. (Contributor) ; Olvera, R. L. (Contributor) ; Oosterlaan, J. (Contributor) ; Ophoff, R. A. (Contributor) ; Pandolfo, M. (Contributor) ; Pantelis, C. (Contributor) ; Pappa, I. (Contributor) ; Penninx, B. (Contributor) ; Pike, G. B. (Contributor) ; Rasser, P. E. (Contributor) ; Rentería, M. E. (Contributor) ; Reppermund, S. (Contributor) ; Rietschel, M. (Contributor) ; Risacher, S. L. (Contributor) ; Romanczuk-Seiferth, N. (Contributor) ; Rose, E. J. (Contributor) ; Sachdev, P. S. (Contributor) ; Sämann, P. G. (Contributor) ; Saykin, A. J. (Contributor) ; Schall, U. (Contributor) ; Schofield, P. R. (Contributor) ; Schramm, S. (Contributor) ; Schumann, G. (Contributor) ; Scott, R. (Contributor) ; Shen, L. (Contributor) ; Sisodiya, S. M. (Contributor) ; Soininen, H. (Contributor) ; Sprooten, E. (Contributor) ; Srikanth, V. (Contributor) ; Steen, V. M. (Contributor) ; Strike, L. T. (Contributor) ; Thalamuthu, A. (Contributor) ; Toga, A. W. (Contributor) ; Tooney, P. (Contributor) ; Tordesillas-Gutiérrez, D. (Contributor) ; Turner, J. A. (Contributor) ; Valdés Hernández, M. D. C. (Contributor) ; van der Meer, D. (Contributor) ; Van der Wee, N. J. A. (Contributor) ; Van Haren, N. E. M. (Contributor) ; van 't Ent, D. (Contributor) ; Veltman, D. J. (Contributor) ; Walter, H. (Contributor) ; Weinberger, D. R. (Contributor) ; Weiner, M. W. (Contributor) ; Wen, W. (Contributor) ; Westlye, L. T. (Contributor) ; Westman, E. (Contributor) ; Winkler, A. M. (Contributor) ; Woldehawariat, G. (Contributor) ; Wright, M. J. (Contributor) ; Wu, J. (Contributor)
2024
Elsevier
Maryland Heights, MO
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Please use a persistent id in citations: doi:10.1016/j.xcrm.2024.101529
Abstract: The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.
Keyword(s): Humans (MeSH) ; Genome-Wide Association Study (MeSH) ; Head: anatomy & histology (MeSH) ; Neoplasms: genetics (MeSH) ; Neoplasms: pathology (MeSH) ; Female (MeSH) ; Male (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Genetic Variation (MeSH) ; Organ Size: genetics (MeSH) ; Signal Transduction: genetics (MeSH) ; Adult (MeSH) ; Genetic Predisposition to Disease (MeSH) ; cancer ; genetics ; genome-wide association study ; head circumference ; head size ; intracranial volume ; meta-analysis
Contributing Institute(s):
- Biomarkers of Dementia in the General Population (AG Grabe)
Research Program(s):
- 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
Appears in the scientific report
2024
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