Inflammation status modulates the effect of host genetic variation on intestinal gene expression in inflammatory bowel disease.
Inflammation status modulates the effect of host genetic variation on intestinal gene expression in inflammatory bowel disease.
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DOI：
10.1038/s41467-021-21458-z
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发表时间：
2021-02-18
影响因子：
16.6
通讯作者：
Weersma RK
中科院分区：
文献类型：
--
作者：
Hu S;Uniken Venema WT;Westra HJ;Vich Vila A;Barbieri R;Voskuil MD;Blokzijl T;Jansen BH;Li Y;Daly MJ;Xavier RJ;Dijkstra G;Festen EA;Weersma RK
超过240个遗传风险位点与炎症性肠病（IBD）相关，但对它们如何促进相关组织中的疾病发展知之甚少。在这里，我们假设宿主遗传变异以炎症依赖的方式影响基因表达，并研究了来自171名IBD患者的炎症和非炎症粘膜的299份速冻肠活检。进行RNA测序，并使用全外显子组测序和全基因组基因分型确定基因型。总共包括28，746个基因和6，894，979个SNP。线性混合模型鉴定了8，881个独立的肠道顺式表达数量性状位点（cis-eQTLs）（FDR < 0.05），互作分析显示了190个炎症依赖性肠道顺式eQTLs（FDR < 0.05），包括已知的IBD风险基因和编码免疫细胞受体和抗体的基因。炎症依赖性顺式eQTL SNPs（eSNPs）主要与免疫细胞类型的流行相互作用。炎症依赖性肠道顺式eQTLs揭示了炎症条件下的遗传易感性，可以帮助识别参与炎症的细胞类型和炎症的潜在途径，这些知识可以指导未来的药物开发和IBD患者的精准医学。炎症性肠病是异质性的，关于潜在的遗传变异如何影响其发展知之甚少。在这里，作者报告说，在炎症性肠病的背景下，肠道炎症调节宿主遗传学对190个基因的肠道粘膜表达的影响。
More than 240 genetic risk loci have been associated with inflammatory bowel disease (IBD), but little is known about how they contribute to disease development in involved tissue. Here, we hypothesized that host genetic variation affects gene expression in an inflammation-dependent way, and investigated 299 snap-frozen intestinal biopsies from inflamed and non-inflamed mucosa from 171 IBD patients. RNA-sequencing was performed, and genotypes were determined using whole exome sequencing and genome wide genotyping. In total, 28,746 genes and 6,894,979 SNPs were included. Linear mixed models identified 8,881 independent intestinal cis-expression quantitative trait loci (cis-eQTLs) (FDR < 0.05) and interaction analysis revealed 190 inflammation-dependent intestinal cis-eQTLs (FDR < 0.05), including known IBD-risk genes and genes encoding immune-cell receptors and antibodies. The inflammation-dependent cis-eQTL SNPs (eSNPs) mainly interact with prevalence of immune cell types. Inflammation-dependent intestinal cis-eQTLs reveal genetic susceptibility under inflammatory conditions that can help identify the cell types involved in and the pathways underlying inflammation, knowledge that may guide future drug development and profile patients for precision medicine in IBD. Inflammatory bowel diseases are heterogeneous, and little is known about how underlying genetic variation can affect their development. Here, the authors report that intestinal inflammation modulates the effect of host genetics on the gut mucosal expression of 190 genes in the context of inflammatory bowel diseases.
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遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
多克隆游离光链：炎症性疾病或治疗靶标的生物标志物？
DOI：
10.3410/m5-4
发表时间：
2013
期刊：
F1000 medicine reports
影响因子：
--
作者：
Brebner JA;Stockley RA
通讯作者：
Stockley RA
影响因子：
30.8
作者：
Marigorta UM;Denson LA;Hyams JS;Mondal K;Prince J;Walters TD;Griffiths A;Noe JD;Crandall WV;Rosh JR;Mack DR;Kellermayer R;Heyman MB;Baker SS;Stephens MC;Baldassano RN;Markowitz JF;Kim MO;Dubinsky MC;Cho J;Aronow BJ;Kugathasan S;Gibson G
通讯作者：
Gibson G
影响因子：
4.3
作者：
Fujii M;Nishida A;Imaeda H;Ohno M;Nishino K;Sakai S;Inatomi O;Bamba S;Kawahara M;Shimizu T;Andoh A
通讯作者：
Andoh A
影响因子：
30.8
作者：
通讯作者：
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