小柯机器人

意大利遗传与生物医学研究所Francesco Cucca等研究人员揭示了自身免疫背后免疫细胞中复杂的遗传特征。相关论文于2020年9月14日在线发表于国际学术期刊《自然—遗传学》。

研究人员报道了3757名撒丁岛人队列中约2200万个变体对731个免疫细胞性状的影响。研究人员在69个位点（其中52个是新的）中检测到459个细胞性状的122个重要（P<1.28×10¹¹）独立关联信号，从而确定了参与细胞调控的几种分子和机制。此外，在36个基因座的53个信号与以前报道的疾病相关信号重叠，主要是自身免疫性疾病，这突出了发病机理中的中间表型。

总的来说，这些发现说明了免疫细胞的复杂遗传调控，其在细胞亚型水平上对自身免疫性疾病风险具有高度选择性。这些结果确定了可靶向药物的途径，并为设计针对自身免疫性疾病的具体疗法提供了依据。

附：英文原文

Title: Complex genetic signatures in immune cells underlie autoimmunity and inform therapy

Author: Valeria Orr, Maristella Steri, Carlo Sidore, Michele Marongiu, Valentina Serra, Stefania Olla, Gabriella Sole, Sandra Lai, Mariano Dei, Antonella Mulas, Francesca Virdis, Maria Grazia Piras, Monia Lobina, Mara Marongiu, Maristella Pitzalis, Francesca Deidda, Annalisa Loizedda, Stefano Onano, Magdalena Zoledziewska, Stephen Sawcer, Marcella Devoto, Myriam Gorospe, Gonalo R. Abecasis, Matteo Floris, Mauro Pala, David Schlessinger, Edoardo Fiorillo, Francesco Cucca

Issue&Volume: 2020-09-14

Abstract: We report on the influence of ~22 million variants on 731 immune cell traits in a cohort of 3,757 Sardinians. We detected 122 significant (P<1.28×1011) independent association signals for 459 cell traits at 69 loci (52 of them novel) identifying several molecules and mechanisms involved in cell regulation. Furthermore, 53 signals at 36 loci overlapped with previously reported disease-associated signals, predominantly for autoimmune disorders, highlighting intermediate phenotypes in pathogenesis. Collectively, our findings illustrate complex genetic regulation of immune cells with highly selective effects on autoimmune disease risk at the cell-subtype level. These results identify drug-targetable pathways informing the design of more specific treatments for autoimmune diseases.

DOI: 10.1038/s41588-020-0684-4

Source: https://www.nature.com/articles/s41588-020-0684-4

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex