免疫细胞中的复杂遗传特征是自身免疫的基础，并为治疗提供信息。
Complex genetic signatures in immune cells underlie autoimmunity and inform therapy.
机构信息
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Cagliari, Italy.
Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy.
出版信息
Nat Genet. 2020 Oct;52(10):1036-1045. doi: 10.1038/s41588-020-0684-4. Epub 2020 Sep 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 × 10) independent association signals for 459 cell traits at 70 loci (53 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.
摘要
我们报告了在一个由 3757 名撒丁岛人组成的队列中，约 2200 万个变体对 731 种免疫细胞特征的影响。我们在 70 个基因座（其中 53 个是新的）检测到了 459 种细胞特征的 122 个显著（P < 1.28×10）独立关联信号，鉴定出了一些涉及细胞调节的分子和机制。此外，36 个基因座的 53 个信号与先前报道的疾病相关信号重叠，主要是自身免疫性疾病，突出了发病机制中的中间表型。总之，我们的研究结果说明了免疫细胞的复杂遗传调控，对自身免疫性疾病风险具有高度选择性的细胞亚型水平效应。这些结果确定了可药物靶向的途径，为自身免疫性疾病的更具体治疗方案的设计提供了信息。
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