Wellcome Trust Sanger Institute, Hinxton, UK.
Am J Hum Genet. 2011 Sep 9;89(3):446-50. doi: 10.1016/j.ajhg.2011.08.001. Epub 2011 Aug 25.
Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 × 10(-8)) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.
骨关节炎（OA）是一种普遍存在的、遗传性的退行性关节疾病，对公共健康有重大影响。我们在一项全基因组关联扫描中使用了基于 1000 基因组计划的内插法，对骨关节炎（3177 例 OA 病例和 4894 例对照）进行了研究，以检测以前未识别的风险位点。我们在 13 号染色体上发现了一个与疾病相关的小变异体集合。通过大规模复制，我们在总共 19041 例 OA 病例和 24504 例欧洲裔对照中建立了与 MCF2L 中 SNP 的可靠关联（rs11842874，联合优势比[95%置信区间]1.17[1.11-1.23]，p=2.1×10(-8)）。这个风险位点代表了 OA 的第三个已确定的信号。MCF2L 调节神经生长因子（NGF），针对 NGF 的人源化单克隆抗体治疗与膝骨关节炎患者的疼痛减轻和功能改善相关。
