Genetic variants for head size share genes and pathways with cancer

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Erasmus University Rotterdam
  • University of Texas Health Science Center at San Antonio
  • National Institutes of Health (NIH)
  • 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
  • Max Planck Institute for Psycholinguistics
  • 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
  • Max Planck Institute for Human Cognitive and Brain Sciences
  • University of Washington
  • Penn Medicine
  • Jülich Research Centre
  • University Hospital Duesseldorf
  • École pratique des Hautes Études (EPHE)
  • University of California at Davis
  • University of Helsinki
  • Folkhalsan
  • Department of Veterans Affairs
  • 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 languageEnglish
Article number101529
Number of pages21
JournalCell Reports Medicine
Volume5
Issue number5
Publication statusPublished - 21 May 2024
Peer-reviewedYes

External IDs

PubMed 38703765
ORCID /0000-0002-1753-7811/work/173516977
ORCID /0000-0003-2132-4445/work/173516987

Keywords

Sustainable Development Goals

Keywords

  • cancer, genetics, genome-wide association study, head circumference, head size, intracranial volume, meta-analysis