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The genetic basis of human height

Nature Reviews Genetics volume 26, pages 604–619 (2025)Cite this article

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Abstract

Human height is a model polygenic trait — additive effects of many individual variants create continuous, genetically determined variation in this phenotype. Height can also be severely affected by single-gene variants in monogenic disorders, often causing severe alterations in stature relative to population averages. Deciphering the genetic basis of height provides understanding into the biology of growth and is also of relevance to disease, as increased or decreased height relative to population averages has been epidemiologically and genetically associated with an altered risk of cancer or cardiometabolic diseases. With recent large-scale genome-wide association studies of human height reaching saturation, its genetic architecture has become clearer. Genes implicated by both monogenic and polygenic studies converge on common developmental or cellular pathways that affect stature, including at the growth plate, a key site of skeletal growth. In this Review, we summarize the genetic contributors to height, from ultra-rare monogenic disorders that severely affect growth to common alleles that act across multiple pathways.

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Fig. 1: Genetic contributions to the spectrum of height.
Fig. 2: Height-associated genes cluster into common processes and pathways that affect activity in the growth plate.
Fig. 3: The determinants of height.
Fig. 4: Bidirectional regulators of height.

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Acknowledgements

The authors thank D. Aiylam, M. Babinksi, S. Vitale (Boston Children’s Hospital) and E. Nielsen Dandoroff (University of Otago) for assistance in compiling monogenic short and tall stature gene lists. J.N.H. is supported by NIH R01DK075787. R.S. is partly supported by NHMRC Leadership Fellow grant 2018081.

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Authors and Affiliations

  1. Department of Biochemistry, University of Otago, Dunedin, New Zealand

    Louise S. Bicknell

  2. Division of Endocrinology, Boston Children’s Hospital, Boston, MA, USA

    Joel N. Hirschhorn

  3. Departments of Paediatrics, Harvard Medical School, Boston, MA, USA

    Joel N. Hirschhorn

  4. Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Joel N. Hirschhorn

  5. Departments of Genetics, Harvard Medical School, Boston, MA, USA

    Joel N. Hirschhorn

  6. Murdoch Children’s Research Institute, Royal Children’s Hospital and University of Melbourne, Parkville, Victoria, Australia

    Ravi Savarirayan

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Bicknell, L.S., Hirschhorn, J.N. & Savarirayan, R. The genetic basis of human height. Nat Rev Genet 26, 604–619 (2025). https://doi.org/10.1038/s41576-025-00834-1

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