Genetic variants for head size share genes and pathways with cancer
Creators: name: Teumer, Alexander
name: Calhoun, Vince D.
name: Nagata, Manabu
name: Poot, Raymond A.
name: van der Lugt, Aad
name: Caspers, Svenja
name: Li, Gloria H.Y.
name: Cecil, Charlotte A.M.
name: Villringer, Arno
name: Reinbold, Céline S.
name: Jahanshad, Neda
name: Nakahara, Soichiro
name: Stein, Jason L.
name: Pawlak, Mikolaj A.
name: Windham, B. Gwen
name: Mäkitie, Outi
name: Le Grand, Quentin
name: Hariri, Ahmad R.
name: Wittfeld, Katharina
name: Vernooij, Meike W.
name: Håberg, Asta K.
name: Ikram, M. Kamran
name: Mühleisen, Thomas W.
name: Dartigues, Jean-François
name: Preda, Adrian
name: Duperron, Marie-Gabrielle
name: Uhlmann, Anne
name: Kämpe, Anders
name: Stein, Dan J.
name: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
name: Schmidt, Reinhold
name: St Pourcain, Beate
name: Patel, Yash
name: Knol, Maria J.
name: Pausova, Zdenka
name: Roshchupkin, Gennady V.
name: Thompson, Paul M.
name: van Dam-Nolen, Dianne H.K.
name: Beiser, Alexa S.
name: Muetzel, Ryan
name: Adams, Hieab H.H.
name: Brunner, Han G.
name: Cairns, Murray J.
name: van Erp, Theo G.M.
name: Tsuchida, Ami
name: Mazoyer, Bernard
name: Helmer, Catherine
name: Satizabal, Claudia L.
name: Avinun, Reut
name: Homuth, Georg
name: The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium
name: Miyamoto, Susumu
name: Sargurupremraj, Muralidharan
name: Werring, David J.
name: Friedrich, Nele
name: Macciardi, Fabio
name: Bis, Joshua C.
name: Sidney, Stephen
name: Kamatani, Yoichiro
name: Seshadri, Sudha
name: van der Auwera, Sandra
name: Houlden, Henry
name: Grabe, Hans J.
name: Reay, William R.
name: Ford, Judith M.
name: Setoh, Kazuya
name: Sim, Kang
name: Lamballais, Sander
name: Cheung, Ching-Lung
name: Debette, Stéphanie
name: Liang, Dan
name: Mosley, Thomas H.
name: Lam, Max
name: Quidé, Yann
name: Launer, Lenore J.
name: Haworth, Simon
name: Yoshida, Kazumichi
name: Bowden, Donald W.
name: Matsuda, Fumihiko
name: Cichon, Sven
name: Enlund-Cerullo, Maria
name: Evans, Tavia E.
name: Beyer, Frauke
name: Shapland, Chin Yang
name: Aygün, Nil
name: Freedman, Barry I.
name: Bryan, R. Nick
name: Lim, Keane
name: Mishra, Aniket
name: Koudstaal, Peter J.
name: Bülow, Robin
name: Andersson, Sture
name: Schreiner, Pamela J.
name: Hostettler, Isabel C.
name: Carrion-Castillo, Amaia
name: Medland, Sarah E.
name: Hsu, Fang-Chi
name: Jack, Clifford R.
name: Ikram, M. Arfan
name: Moebus, Susanne
name: Hoffmann, Per
name: Amod, Alyssa R.
name: Crivello, Fabrice
name: Green, Melissa J.
name: Fornage, Myriam
name: Catheline, Gwenaëlle
name: Scholz, Markus
name: Paus, Tomas
name: Dalvie, Shareefa
name: Knodt, Annchen R.
name: DeCarli, Charles
name: Jian, Xueqiu
name: Teunissen, Mariël W.A.
name: Franke, Barbara
name: Bos, Daniel
name: Li, Shuo
name: Lewis, Cora E.
name: Shin, Jean
name: White, Tonya
name: Jockwitz, Christiane
name: Yang, Qiong
name: Palmer, Nicholette D.
name: Tabara, Yasuharu
name: Atkins, Joshua R.
name: Witte, A. Veronica
name: Longstreth, W.T.
Publisher: name: Elsevier
Year: 2024

description: 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.