School of Medicine Publications and Presentations
Document Type
Article
Publication Date
5-21-2024
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.
Recommended Citation
Knol, M. J., Poot, R. A., Evans, T. E., Satizabal, C. L., Mishra, A., Sargurupremraj, M., van der Auwera, S., 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., Håberg, A. K., … Adams, H. H. H. (2024). Genetic variants for head size share genes and pathways with cancer. Cell reports. Medicine, 5(5), 101529. https://doi.org/10.1016/j.xcrm.2024.101529
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Cell reports. Medicine
DOI
https://doi.org/10.1016/j.xcrm.2024.101529
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Copyright 2024 The Author(s).This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).