美国阿拉巴马大学伯明翰分校Merry-Lynn N. McDonald等研究人员共同合作近期取得重要工作进展，他们通过在百万老兵计划和英国生物银行的多血统分析中发现与骨关节炎相关的新遗传位点。该项研究成果2022年11月21日在线发表于《自然—遗传学》杂志上。

研究人员利用百万老兵计划和英国生物银行484374名参与者的独特资源来解决这一差距。分析包括欧洲、非洲、亚洲和西班牙裔的参与者。研究人员在10个位点发现了骨关节炎相关的基因变异，并复制了先前骨关节炎研究的结果。研究人员还提出一些证据，表明某些骨关节炎相关区域与人群祖先有很强的相关性。药物再利用分析揭示出几种药物类别靶点的富集，并为抗癫痫药对骨关节炎疼痛有益作用的病因提供了见解。

据介绍，骨关节炎是一种常见的进行性关节疾病。由于没有有效的医疗干预措施，骨关节炎往往发展到末期，只能选择手术，如全关节置换术。更深入地了解骨关节炎的遗传基因影响对于制定有针对性的个性化治疗方法是至关重要的。目前为止，还没有关于骨关节炎的大规模多血统遗传学研究。

附：英文原文

Title: Novel genetic loci associated with osteoarthritis in multi-ancestry analyses in the Million Veteran Program and UK Biobank

Author: McDonald, Merry-Lynn N., Lakshman Kumar, Preeti, Srinivasasainagendra, Vinodh, Nair, Ashwathy, Rocco, Alison P., Wilson, Ava C., Chiles, Joe W., Richman, Joshua S., Pinson, Sarah A., Dennis, Richard A., Jagadale, Vivek, Brown, Cynthia J., Pyarajan, Saiju, Tiwari, Hemant K., Bamman, Marcas M., Singh, Jasvinder A.

Issue&Volume: 2022-11-21

Abstract: Osteoarthritis is a common progressive joint disease. As no effective medical interventions are available, osteoarthritis often progresses to the end stage, in which only surgical options such as total joint replacement are available. A more thorough understanding of genetic influences of osteoarthritis is essential to develop targeted personalized approaches to treatment, ideally long before the end stage is reached. To date, there have been no large multiancestry genetic studies of osteoarthritis. Here, we leveraged the unique resources of 484,374 participants in the Million Veteran Program and UK Biobank to address this gap. Analyses included participants of European, African, Asian and Hispanic descent. We discovered osteoarthritis-associated genetic variation at 10 loci and replicated findings from previous osteoarthritis studies. We also present evidence that some osteoarthritis-associated regions are robust to population ancestry. Drug repurposing analyses revealed enrichment of targets of several medication classes and provide potential insight into the etiology of beneficial effects of antiepileptics on osteoarthritis pain.

DOI: 10.1038/s41588-022-01221-w

Source: https://www.nature.com/articles/s41588-022-01221-w