Genetic variants for head size share genes and pathways with cancer

The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium

    Research output: Contribution to journalArticlepeer-review


    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.

    Original languageEnglish
    Article number101529
    JournalCell Reports Medicine
    Issue number5
    Publication statusPublished or Issued - 3 May 2024


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

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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