Steno Diabetes Center Copenhagen, Gentofte DK2820, Denmark.
Department of Biology, The Bioinformatics Center, University of Copenhagen, Copenhagen DK2200, Denmark.
Hum Mol Genet. 2021 Apr 27;30(5):393-409. doi: 10.1093/hmg/ddab023.
Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
白细胞介素 6（IL-6）是一种具有促炎和抗炎特性的多功能细胞因子，其遗传率估计高达 61%。血液中 IL-6 的循环水平与复杂疾病发病机制的风险增加有关。我们进行了一项两阶段的、基于全基因组关联研究（GWAS）的发现和复制，对循环血清 IL-6 水平进行了研究，包括多达 67428 名（ndiscovery=52654 名，nreplication=14774 名）欧洲血统的个体。基于逆方差固定效应的发现元分析，随后进行复制，导致鉴定出两个独立的位点，即位于染色体 2q14 上的 IL1F10/IL1RN rs6734238（Pcombined=1.8×10-11）和位于 Chr6p21 上的 HLA-DRB1/DRB5 rs660895（Pcombined=1.5×10-10），这两个位点在所有样本的合并元分析中都得到了鉴定。我们还复制了位于 Chr1q21 上的 IL6R rs4537545 位点（Pcombined=1.2×10-122）。我们的研究确定了循环 IL-6 水平的新位点，揭示了新的免疫和炎症途径，这些途径可能影响 IL-6 的病理生物学。
