Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknown. Here we report the results of a genome-wide genetic study of blood concentration of ten cytokines, including the hitherto unexplored calcium-binding protein (S100B). The study leverages a unique sample of neonatal blood spots from 9,459 Danish subjects from the iPSYCH initiative. We estimate the SNP-heritability of marker levels as ranging from essentially zero for Erythropoietin (EPO) up to 73% for S100B. We identify and replicate 16 associated genomic regions (p < 5 x 10⁻⁹), of which four are novel. We show that the associated variants map to enhancer elements, suggesting a possible transcriptional effect of genomic variants on the cytokine levels. The identification of the genetic architecture underlying the basic levels of cytokines is likely to prompt studies investigating the relationship between cytokines and complex disease. Our results also suggest that the genetic architecture of cytokines is stable from neonatal to adult life.

循环炎症标记物对人类健康和疾病至关重要，在癌症以及心血管，代谢，免疫和神经精神疾病中，它们经常失调或功能异常。但是，对循环炎症标记物水平的生理变化的遗传贡献在很大程度上是未知的。在这里，我们报告了对十种细胞因子的血液浓度进行全基因组遗传研究的结果，其中包括迄今尚未探索的钙结合蛋白（S100B）。该研究利用了来自iPSYCH计划的9459名丹麦受试者的新生儿血斑的独特样本。我们估计标记物水平的SNP遗传力范围从促红细胞生成素（EPO）的基本为零到S100B的73％。我们确定并复制了16个相关的基因组区域（p <5 x 10 ^-9），其中四个是新颖的。我们表明，相关的变体映射到增强子元素，表明基因组变体对细胞因子水平的可能的转录作用。鉴定基本细胞因子水平的遗传结构很可能促使研究细胞因子与复杂疾病之间关系的研究。我们的结果还表明，从新生儿到成年，细胞因子的遗传结构都是稳定的。