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 × 10⁻¹¹) 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.

我们报告了约 2200 万种变异对 3,757 名撒丁岛人的 731 种免疫细胞特征的影响。我们在 69 个位点（其中 52 个是新的）检测到 122 个显着 ( P  < 1.28 × 10 ^-11 ) 的 459 个细胞特征的独立关联信号，确定了涉及细胞调节的几种分子和机制。此外，36 个位点的 53 个信号与先前报道的疾病相关信号重叠，主要针对自身免疫性疾病，突出了发病机制中的中间表型。总的来说，我们的研究结果说明了免疫细胞的复杂遗传调控，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影响。这些结果确定了药物靶向途径，为自身免疫性疾病更具体的治疗设计提供了信息。