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

Autor: Sethi A; Calico Life Sciences, LLC, South San Francisco, CA, 94080, USA. anurag@calicolabs.com., Ruby JG; Calico Life Sciences, LLC, South San Francisco, CA, 94080, USA., Veras MA; Calico Life Sciences, LLC, South San Francisco, CA, 94080, USA., Telis N; Calico Life Sciences, LLC, South San Francisco, CA, 94080, USA., Melamud E; Calico Life Sciences, LLC, South San Francisco, CA, 94080, USA. eugene@calicolabs.com.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 08; Vol. 14 (1), pp. 2644. Date of Electronic Publication: 2023 May 08.
DOI: 10.1038/s41467-023-38279-x
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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