Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands.
Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands.
Bone. 2019 Sep;126:2-10. doi: 10.1016/j.bone.2019.04.005. Epub 2019 Apr 10.
Osteoporosis and fracture risk are common complex diseases, caused by an interaction of numerous disease susceptibility genes and environmental factors. With the advances in genomic technologies, large-scale genome-wide association studies (GWAS) have been performed which have broadened our understanding of the genetic architecture and biological mechanisms of complex disease. Currently, more than ~90 loci have been found associated with DXA derived bone mineral density (BMD), over ~500 loci with heel estimated BMD and several others with other less widely available bone parameters such as bone geometry, shape, and microarchitecture. Notably, several of the pathways identified by the GWAS efforts correspond to pathways that are currently targeted for the treatment of osteoporosis. Overall, tremendous progress in the field of the genetics of osteoporosis has been achieved with the discovery of WNT16, EN1, DAAM2, and GPC6 among others. Assessment of the function and biological mechanisms of the remaining genes may further untangle the complex genetic landscape of osteoporosis and fracture risk. With this review we aimed to provide a general overview of the existing GWAS studies on osteoporosis traits and fracture risk.
骨质疏松症和骨折风险是常见的复杂疾病，由许多疾病易感性基因和环境因素相互作用引起。随着基因组技术的进步，已经进行了大规模的全基因组关联研究（GWAS），这拓宽了我们对复杂疾病遗传结构和生物学机制的理解。目前，已经发现了90 多个与双能 X 线吸收法（DXA）测量的骨矿物质密度（BMD）相关的位点，超过500 个与足跟估计 BMD 相关的位点，还有一些与其他不太广泛可用的骨参数相关，如骨几何形状、形状和微观结构。值得注意的是，GWAS 研究中确定的几个途径与目前骨质疏松症治疗的靶点途径相对应。总的来说，随着 WNT16、EN1、DAAM2 和 GPC6 等基因的发现，骨质疏松症遗传学领域取得了巨大进展。评估其余基因的功能和生物学机制可能会进一步理清骨质疏松症和骨折风险的复杂遗传景观。通过这篇综述，我们旨在提供关于骨质疏松症特征和骨折风险的现有 GWAS 研究的概述。
