| Title: |
Genetic variants for head size share genes and pathways with cancer |
| Authors: |
Knol, MJ; Poot, RA; Evans, TE; Satizabal, CL; Mishra, A; Sargurupremraj, M; van der Auwera, S; Duperron, MG; Jian, X; Hostettler, IC; van Dam-Nolen, DHK; Lamballais, S; Pawlak, MA; Lewis, CE; Carrion-Castillo, A; van Erp, TGM; Reinbold, CS; Shin, J; Scholz, M; Håberg, AK; Kämpe, A; Li, GHY; Avinun, R; Atkins, JR; Hsu, FC; Amod, AR; Lam, M; Tsuchida, A; Teunissen, MWA; Aygün, N; Patel, Y; Liang, D; Beiser, AS; Beyer, F; Bis, JC; Bos, D; Bryan, RN; Bülow, R; Caspers, S; Catheline, G; Cecil, CAM; Dalvie, S; Dartigues, JF; DeCarli, C; Enlund-Cerullo, M; Ford, JM; Franke, B; Freedman, BI; Friedrich, N; Green, MJ; Haworth, S; Helmer, C; Hoffmann, P; Homuth, G; Ikram, MK; Jack, CR; Jahanshad, N; Jockwitz, C; Kamatani, Y; Knodt, AR; Li, S; Lim, K; Longstreth, WT; Macciardi, F; Amouyel, P; Arfanakis, K; Aribisala, BS; Bastin, ME; Chauhan, G; Chen, C; Cheng, CY; de Jager, PL; Deary, IJ; Fleischman, DA; Gottesman, RF; Gudnason, V; Hilal, S; Hofer, E; Janowitz, D; Jukema, JW; Liewald, DCM; Lopez, LM; Lopez, O; Luciano, M; Martinez, O; Niessen, WJ; Nyquist, P; Rotter, JI; Rundek, T; Sacco, RL; Schmidt, H; Tiemeier, H; Trompet, S; van der Grond, J; Völzke, H; Wardlaw, JM; Yanek, L; Yang, J; Agartz, I; Alhusaini, S; Quide, Yann; Reppermund, Simone; Carr, Vaughan; Reay, William Robert; Mather, Karen; Thalamuthu, Anbu; Brodaty, Henry; Wen, Wei |
| Source: |
urn:ISSN:2666-3791 ; Cell Reports Medicine, 5, 5, 101529 |
| Publisher Information: |
Elsevier |
| Publication Year: |
2024 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
32 Biomedical and Clinical Sciences; Human Genome; Genetics; Stem Cell Research; Neurosciences; Biotechnology; Cancer; 2.1 Biological and endogenous factors; 1.1 Normal biological development and functioning; Neurological; Humans; Genome-Wide Association Study; Head; Neoplasms; Female; Male; Polymorphism; Single Nucleotide; Genetic Variation; Organ Size; Signal Transduction; Adult; Genetic Predisposition to Disease; head circumference; head size; intracranial volume; meta-analysis; Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium; Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium; anzsrc-for: 32 Biomedical and Clinical Sciences |
| 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/102366; https://doi.org/10.1016/j.xcrm.2024.101529 |
| DOI: |
10.1016/j.xcrm.2024.101529 |
| Availability: |
https://hdl.handle.net/1959.4/102366; https://unsworks.unsw.edu.au/bitstreams/5b200405-88af-43d4-ad77-8975b76f5105/download; https://doi.org/10.1016/j.xcrm.2024.101529 |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read |
| Accession Number: |
edsbas.954534C2 |
| Database: |
BASE |