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.

弥漫性特发性骨质增生症 (DISH) 是一种相邻椎骨通过形成骨赘而融合的病症。这种情况的遗传和流行病学病因尚不清楚。在这里，我们实施了一种机器学习算法来评估英国生物银行成像队列中约 40,000 次横向 DXA 扫描中病理学的患病率和严重程度。我们发现 DISH 非常普遍，年龄在 45 岁以上，约 20% 的男性和约 8% 的女性患有多处骨赘。令人惊讶的是，我们发现 DISH 在整个骨骼系统中与骨矿物质密度和含量增加有很强的表型和遗传关联。遗传关联分析确定了 10 个与 DISH 相关的位点，包括多个参与骨重建的基因（RUNX2、IL11、GDF5、CCDC91、NOG 和 ROR2). 总的来说，这项研究描述了 DISH 的遗传学，并将过度活跃的成骨作用作为病理学的关键驱动因素。