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. 2023 May 8;14:2644. doi: 10.1038/s41467-023-38279-x

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — In addition to male sex and age, pre-existing conditions such T2D, obesity, and osteoarthritis are risk factors associated with DISH. Genetic analysis (GWAS, colocalization, and Mendelian randomization) points to genes involved in overactive osteogenesis as drivers of the pathology (highlighted in orange). The increase in osteogenesis, and consequence in increases in BMD and BMC measures is observed throughout the entire body. Molecular mechanisms likely involve gain of function in multiple signaling pathways such Wnt signaling, IL11 signaling, and BMP-signaling. Conversely, loss of inhibitory BMP proteins such as Noggin and CRDL2 likely increases BMP-signaling. In prognostic outcomes, DISH is associated with increased risk of metabolic and sleep disorder diagnoses.