Knol, Maria J;
Poot, Raymond A;
Evans, Tavia E;
Satizabal, Claudia L;
Mishra, Aniket;
Sargurupremraj, Muralidharan;
Van der Auwera, Sandra;
... Adams, Hieab HH; + view all
(2024)
Genetic variants for head size share genes and pathways with cancer.
Cell Reports Medicine
, Article 101529. 10.1016/j.xcrm.2024.101529.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Genetic variants for head size share genes and pathways with cancer |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.xcrm.2024.101529 |
| Publisher version: | http://dx.doi.org/10.1016/j.xcrm.2024.101529 |
| Language: | English |
| Additional information: | Copyright © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Genetics; genome-wide association study; head size; intracranial volume; head circumference; cancer; meta-analysis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10191918 |
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