Identification of sequence variants influencing immunoglobulin levels
Identification of sequence variants influencing immunoglobulin levels
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DOI：
10.1038/ng.3897
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发表时间：
2017-08-01
期刊：
影响因子：
30.8
通讯作者：
Stefansson, Kari
中科院分区：
文献类型：
--
作者：
Jonsson, Stefan;Sveinbjornsson, Gardar;Stefansson, Kari
免疫球蛋白是适应性体液免疫系统的效应分子。在一项针对19219人的全基因组关联研究中，我们发现了38个新的变异体，并重复验证了5个已知的与IgA、IgG或IgM水平或复合免疫球蛋白特性相关的变异体，这些变异体由32个基因座所解释。这些基因座的变异体还影响自身免疫性疾病和血液恶性肿瘤的风险，并影响血细胞的发育。值得注意的关联包括：RUNX3的一个罕见变异体通过改变异构体比例降低IgA水平（rs188468174[C>T]：P = 8.3×10⁻⁵⁵，β = -0.90标准差）；FCGR2B的一个罕见的框内缺失使IgG无法与编码的受体结合（p.Asn106del：P = 4.2×10⁻⁸，β = 1.03标准差）；4个IGH基因座变异体影响类别转换；以及10个与HLA区域的新关联。我们的研究结果为体液免疫的调节提供了新的见解。
Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 x 10(-55), beta = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 x 10(-8), beta = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.