Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
Curr Opin Rheumatol. 2011 Sep;23(5):479-83. doi: 10.1097/BOR.0b013e3283493ff0.
A number of reasonably powered osteoarthritis genome-wide association scans are now in the final phases of their analysis, leaving us all with baited breath. This review highlights some of the osteoarthritis signals and subsequent insights that have emerged from the candidate studies and smaller scale scans that have preceded these more powered studies, and which could therefore be considered as appetizers to the hopeful treats to follow.
If one applies the strict criteria of genome-wide significance thresholds, only two current signals pass muster: GDF5 and 7p22. If one relaxes slightly, other signals emerge, such as DIO2, SMAD3 and ASPN. After these, however, we enter the realm where faith takes precedence.
The search for osteoarthritis susceptibility loci has not been as successful as many had anticipated. This reflects many factors, including the heterogeneous nature of the disease, the tendency to use less severe phenotypes in genetic searches and the reliance on underpowered studies. We do, however, have some successes and in the very near future others will emerge from the more powered scans. Hopefully, combining the current with the new will help our attempts to understand the cause of this complex, common arthritis.
目前，多项具有相当影响力的骨关节炎全基因组关联扫描已进入分析的最后阶段，让我们都充满期待。本综述强调了一些来自候选研究和较小规模扫描的骨关节炎信号及其后续见解，这些研究为更具影响力的研究提供了前期探索，可被视为对后续研究的期望。
如果严格按照全基因组意义标准筛选，仅有两个信号符合要求：GDF5 和 7p22。如果稍微放宽标准，其他信号也会出现，如 DIO2、SMAD3 和 ASPN。但在此之后，我们就进入了需要信仰的领域。
骨关节炎易感基因位点的研究并未如许多人预期的那样成功。这反映了许多因素，包括疾病的异质性、遗传研究中倾向于使用较轻表型以及依赖于研究效能不足。然而，我们确实取得了一些成功，而且在不久的将来，更多的全基因组关联扫描也将取得新的成功。希望将目前的研究与新的研究相结合，有助于我们了解这种复杂常见关节炎的病因。
