35.1万人多族裔基因分析发现29个类风湿关节炎新位点 锁定203个高置信效应基因
《自然·通讯》11月14日发表一项多族裔基因研究。研究团队整合已发表与新数据集，对351,498人进行全基因组关联荟萃分析，其中类风湿关节炎病例39,600例、对照311,898例。
分析共发现29个新的类风湿关节炎易感位点，并把关联信号系统分为东亚与欧洲人群之间的群体特异、群体主导和群体共享三类。
通过贝叶斯精细定位与功能注释，研究在新位点中优先锁定67个后验包含概率大于0.1的候选因果变异，包括 SLC27A6 错义变异 rs137898880 和 STIM1 的3′非翻译区变异 rs3750996。
结合遗传与生物学证据的基因优先排序框架共确定203个高置信效应基因，其中16个位于新位点内，包括 IFI16、AIM2、RGS1、ITPKB、CD80、RHOH、NFKB1、SIK3 和 CCND2。论文题为《多族裔遗传分析揭示29个类风湿关节炎新位点、效应基因与药物再利用机会》，作者包括 Kwon、Bang、Ha 等研究人员。
关联：马萨诸塞州波士顿市中资背景药企Lynk 公布三期长期积极结果，类风湿新药疗效维持至76周
Multi-Ancestry Analysis of 351,498 People Finds 29 Novel Rheumatoid Arthritis Loci and 203 Effector Genes
Nature Communications on November 14 published a multi-ancestry genetic study of rheumatoid arthritis (RA). The team integrated published and new datasets in genome-wide association meta-analyses of 351,498 individuals, comprising 39,600 RA cases and 311,898 controls.
The analysis identified 29 novel RA susceptibility loci and systematically classified association signals as population-specific, population-dominant, or population-shared between East Asian and European populations.
Bayesian fine-mapping and functional annotation prioritized 67 putative causal variants with posterior inclusion probability above 0.1 in the novel loci, including an SLC27A6 missense variant (rs137898880) and a STIM1 3′ UTR variant (rs3750996).
A gene-prioritization framework combining genetic and biological evidence identified 203 high-confidence effector genes, 16 of which reside in novel loci, including IFI16, AIM2, RGS1, ITPKB, CD80, RHOH, NFKB1, SIK3 and CCND2. The paper, by Kwon, Bang, Ha and colleagues, is titled 'Multi-ancestry genetic analysis reveals 29 novel rheumatoid arthritis loci, effector genes and drug repurposing opportunities'.
来源：《自然·通讯》
发布：GSM·美国（发布链接）
图片来源：图：类风湿关节炎患者的双手（资料图）。来源：Wikimedia Commons，CC0。 / Photo: The hands of a rheumatoid arthritis patient (file photo). Source: Wikimedia Commons, CC0.
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