Sex influences eQTL effects of SLE and Sjögren's syndrome-associated genetic polymorphisms.
Sex influences eQTL effects of SLE and Sjögren's syndrome-associated genetic polymorphisms.
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DOI：
10.1186/s13293-017-0153-7
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发表时间：
2017-10-25
影响因子：
7.9
通讯作者：
Wahren-Herlenius M
中科院分区：
文献类型：
--
作者：
Lindén M;Ramírez Sepúlveda JI;James T;Thorlacius GE;Brauner S;Gómez-Cabrero D;Olsson T;Kockum I;Wahren-Herlenius M
系统性红斑狼疮（SLE）和原发性Sjögren综合征（pSS）是一种自身免疫性疾病，其特征是自身抗体、B细胞失调，女性与男性的发病率明显较高。全基因组关联研究已经确定了这两种疾病的几个易感性snp。基因组中的许多snp是表达数量性状位点（eQTLs），具有上下文依赖效应。假设性别是一个生物学背景，我们研究了SLE/pSS snp是否在B细胞中作为等效qtl，并使用疾病靶向方法来了解它们是否表现出性别特异性效应。我们使用了来自125名男性和162名女性的原代B细胞的全基因组基因型和基因表达数据。使用MatrixEQTL R包在22个已建立的SLE和/或pSS易感性snp的基因组窗口内鉴定2mb内的eqtl。为了找到性别特异性的eqtl，我们使用了带有SNP *性别相互作用项的线性模型。我们发现10个snp影响16个不同基因的表达（FDR < 0.05）。rs7574865-INPP1、rs7574865-MYO1B、rs4938573-CD3D、rs11755393-SNRPC和rs4963128-PHRF1是免疫室和B细胞的新观察结果。通过分析SNP *性别相互作用项，我们确定了6个在女性中与男性相比表达差异的基因，这取决于SLE/ pss相关SNP的基因型：SLC39A8 （BANK1位点）、CD74 （TNIP1位点）、PXK、CTSB （BLK/FAM167A位点）、ARCN1 （CXCR5位点）和DHX9 （NCF2位点）。我们发现了几个未知的SLE/ pss相关遗传多态性的性别特异性eQTL效应，并为基因-性别相互作用如何导致系统性自身免疫性疾病的性别偏见提供了新的见解。本文的在线版本（10.1186/s13293-017-0153-7）包含补充材料，授权用户可使用。
Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B cells, and notably high female-to-male incidence ratios. Genome-wide association studies have identified several susceptibility SNPs for both diseases. Many SNPs in the genome are expression quantitative trait loci (eQTLs), with context-dependent effects. Assuming that sex is a biological context, we investigated whether SLE/pSS SNPs act as eQTLs in B cells and used a disease-targeted approach to understand if they display sex-specific effects. We used genome-wide genotype and gene expression data from primary B cells from 125 males and 162 females. The MatrixEQTL R package was used to identify eQTLs within a genomic window of 2 Mb centered on each of 22 established SLE and/or pSS susceptibility SNPs. To find sex-specific eQTLs, we used a linear model with a SNP * sex interaction term. We found ten SNPs affecting the expression of 16 different genes (FDR < 0.05). rs7574865-INPP1, rs7574865-MYO1B, rs4938573-CD3D, rs11755393-SNRPC, and rs4963128-PHRF1 were novel observations for the immune compartment and B cells. By analyzing the SNP * sex interaction terms, we identified six genes with differentially regulated expression in females compared to males, depending on the genotype of SLE/pSS-associated SNPs: SLC39A8 (BANK1 locus), CD74 (TNIP1 locus), PXK, CTSB (BLK/FAM167A locus), ARCN1 (CXCR5 locus), and DHX9 (NCF2 locus). We identified several unknown sex-specific eQTL effects of SLE/pSS-associated genetic polymorphisms and provide novel insight into how gene-sex interactions may contribute to the sex bias in systemic autoimmune diseases. The online version of this article (10.1186/s13293-017-0153-7) contains supplementary material, which is available to authorized users.
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作者：
Cunninghame Graham DS;Morris DL;Bhangale TR;Criswell LA;Syvänen AC;Rönnblom L;Behrens TW;Graham RR;Vyse TJ
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de Bakker, Paul I. W.
6q23 上 TNFAIP3 附近的遗传变异与系统性红斑狼疮相关。
影响因子：
30.8
作者：
Graham, Robert R.;Cotsapas, Chris;Davies, Leela;Hackett, Rachel;Lessard, Christopher J.;Leon, Joanlise M.;Burtt, Noel P.;Guiducci, Candace;Parkin, Melissa;Gates, Casey;Plenge, Robert M.;Behrens, Timothy W.;Wither, Joan E.;Rioux, John D.;Fortin, Paul R.;Graham, Deborah Cunninghame;Wong, Andrew K.;Vyse, Timothy J.;Daly, Mark J.;Altshuler, David;Moser, Kathy L.;Gaffney, Patrick M.
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Gaffney, Patrick M.