Genetic variants for head size share genes and pathways with cancer
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Erasmus University Rotterdam
- University of Texas Health Science Center at San Antonio
- Boston University
- Bordeaux population Health
- University of Greifswald
- German Center for Neurodegenerative Diseases (DZNE)
- University of Texas Health Science Center at Houston
- University College London
- Ludwig Maximilian University of Munich
- Cantonal Hospital St. Gallen
- University of Medical Sciences Poznan
- Radboud University Nijmegen
- University of Alabama at Birmingham
- University of California at Irvine
- University of Basel
- Zurich University of Applied Sciences (ZHAW)
- University of Toronto
- Leipzig University
- University Hospital Leipzig
- Norwegian University of Science and Technology
- St Olavs' University Hospital
- Karolinska Institutet
- The University of Hong Kong
- Duke University
- University of Newcastle
- Hunter Medical Research Institute (HMRI)
- Wake Forest University
- TUD Dresden University of Technology
- Singapore Institute of Mental Health
- Nanyang Technological University
- Université de Bordeaux
- Maastricht University Medical Centre (UMC+)
- University of North Carolina at Chapel Hill
- University of Washington
- Penn Medicine
- University Hospital Duesseldorf
- École pratique des Hautes Études (EPHE)
- University of California at Davis
- University of Helsinki
- Folkhalsan
- University of California at San Francisco
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.
Details
Original language | English |
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Article number | 101529 |
Number of pages | 21 |
Journal | Cell Reports Medicine |
Volume | 5 |
Issue number | 5 |
Publication status | Published - 21 May 2024 |
Peer-reviewed | Yes |
External IDs
PubMed | 38703765 |
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ORCID | /0000-0002-1753-7811/work/173516977 |
ORCID | /0000-0003-2132-4445/work/173516987 |
Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- cancer, genetics, genome-wide association study, head circumference, head size, intracranial volume, meta-analysis