Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors
Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors
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DOI：
10.1016/j.ajhg.2016.11.007
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发表时间：
2017-01-05
影响因子：
9.8
通讯作者：
Raitakari, Olli T.
中科院分区：
文献类型：
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作者：
Ahola-Olli, Ari V.;Wurtz, Peter;Raitakari, Olli T.
循环细胞因子和生长因子是炎症的调节因子，并与自身免疫性和代谢性疾病有关。在这项对多达8,293名芬兰人进行的全基因组关联研究（GWAS）中，我们确定了一种或多种细胞因子的27个全基因组显著位点（p < 1.2 x 10（-9））。15个相关的变异体在全血中有表达的数量性状位点。我们提供遗传工具来阐明细胞因子信号传导和上游炎症在免疫相关疾病和其他慢性疾病中的因果作用。我们进一步将炎症标志物与先前与自身免疫性疾病（如克罗恩病、多发性硬化和溃疡性结肠炎）相关的变体联系起来，从而阐明了这些疾病的分子机制，并提出了潜在的药物靶点。
Circulating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) of up to 8,293 Finns we identified 27 genome-widely significant loci (p < 1.2 x 10(-9)) for one or more cytokines. Fifteen of the associated variants had expression quantitative trait loci in whole blood. We provide genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link inflammatory markers with variants previously associated with autoimmune diseases such as Crohn disease, multiple sclerosis, and ulcerative colitis and hereby elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets.