TY - JOUR
T1 - Genetic variants for head size share genes and pathways with cancer
AU - The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
AU - The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium
AU - Knol, Maria J.
AU - Poot, Raymond A.
AU - Evans, Tavia E.
AU - Satizabal, Claudia L.
AU - Mishra, Aniket
AU - Sargurupremraj, Muralidharan
AU - van der Auwera, Sandra
AU - Duperron, Marie Gabrielle
AU - Jian, Xueqiu
AU - Hostettler, Isabel C.
AU - van Dam-Nolen, Dianne H.K.
AU - Lamballais, Sander
AU - Pawlak, Mikolaj A.
AU - Lewis, Cora E.
AU - Carrion-Castillo, Amaia
AU - van Erp, Theo G.M.
AU - Reinbold, Céline S.
AU - Shin, Jean
AU - Scholz, Markus
AU - Håberg, Asta K.
AU - Kämpe, Anders
AU - Li, Gloria H.Y.
AU - Avinun, Reut
AU - Atkins, Joshua R.
AU - Hsu, Fang Chi
AU - Amod, Alyssa R.
AU - Lam, Max
AU - Tsuchida, Ami
AU - Teunissen, Mariël W.A.
AU - Aygün, Nil
AU - Patel, Yash
AU - Liang, Dan
AU - Beiser, Alexa S.
AU - Beyer, Frauke
AU - Bis, Joshua C.
AU - Bos, Daniel
AU - Bryan, R. Nick
AU - Bülow, Robin
AU - Caspers, Svenja
AU - Catheline, Gwenaëlle
AU - Cecil, Charlotte A.M.
AU - Dalvie, Shareefa
AU - Dartigues, Jean François
AU - DeCarli, Charles
AU - Enlund-Cerullo, Maria
AU - Ford, Judith M.
AU - Franke, Barbara
AU - Freedman, Barry I.
AU - Friedrich, Nele
AU - Hottenga, Jouke Jan
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/5/21
Y1 - 2024/5/21
N2 - 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.
AB - 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.
KW - cancer
KW - genetics
KW - genome-wide association study
KW - head circumference
KW - head size
KW - intracranial volume
KW - meta-analysis
UR - https://www.scopus.com/pages/publications/85193294036
U2 - 10.1016/j.xcrm.2024.101529
DO - 10.1016/j.xcrm.2024.101529
M3 - Article
C2 - 38703765
AN - SCOPUS:85193294036
SN - 2666-3791
VL - 5
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 5
M1 - 101529
ER -