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Genetics implicates overactive osteogenesis in the development of diffuse idiopathic skeletal hyperostosis

Author

Listed:
  • Anurag Sethi

    (Calico Life Sciences, LLC)

  • J. Graham Ruby

    (Calico Life Sciences, LLC)

  • Matthew A. Veras

    (Calico Life Sciences, LLC)

  • Natalie Telis

    (Calico Life Sciences, LLC)

  • Eugene Melamud

    (Calico Life Sciences, LLC)

Abstract

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition where adjacent vertebrae become fused through formation of osteophytes. The genetic and epidemiological etiology of this condition is not well understood. Here, we implemented a machine learning algorithm to assess the prevalence and severity of the pathology in ~40,000 lateral DXA scans in the UK Biobank Imaging cohort. We find that DISH is highly prevalent, above the age of 45, ~20% of men and ~8% of women having multiple osteophytes. Surprisingly, we find strong phenotypic and genetic association of DISH with increased bone mineral density and content throughout the entire skeletal system. Genetic association analysis identified ten loci associated with DISH, including multiple genes involved in bone remodeling (RUNX2, IL11, GDF5, CCDC91, NOG, and ROR2). Overall, this study describes genetics of DISH and implicates the role of overactive osteogenesis as a key driver of the pathology.

Suggested Citation

  • Anurag Sethi & J. Graham Ruby & Matthew A. Veras & Natalie Telis & Eugene Melamud, 2023. "Genetics implicates overactive osteogenesis in the development of diffuse idiopathic skeletal hyperostosis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38279-x
    DOI: 10.1038/s41467-023-38279-x
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    1. Tune H. Pers & Juha M. Karjalainen & Yingleong Chan & Harm-Jan Westra & Andrew R. Wood & Jian Yang & Julian C. Lui & Sailaja Vedantam & Stefan Gustafsson & Tonu Esko & Tim Frayling & Elizabeth K. Spel, 2015. "Biological interpretation of genome-wide association studies using predicted gene functions," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
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