Blood：新发现16个静脉血栓栓塞的遗传易感位点！

2019-08-18 MedSci MedSci原创

静脉血栓栓塞(VTE)是一种高发病率和高死亡率的疾病。为进一步深入了解促进VTE发生的生理机制，研究人员对VTE患者进行全基因组关联研究(GWAS)和全基因组关联研究(TWAS)和基于全血和肝脏基因表达的全转录组关联研究(TWAS)。研究人员对18个队列的30 234位VTE患者和172 122位对照的GWAS数据进行Meta分析，来评估12 923 718个遗传变异与VTE的相关性。研究人员从全

静脉血栓栓塞(VTE)是一种高发病率和高死亡率的疾病。为进一步深入了解促进VTE发生的生理机制，研究人员对VTE患者进行全基因组关联研究(GWAS)和全基因组关联研究(TWAS)和基于全血和肝脏基因表达的全转录组关联研究(TWAS)。

研究人员对18个队列的30 234位VTE患者和172 122位对照的GWAS数据进行Meta分析，来评估12 923 718个遗传变异与VTE的相关性。研究人员从全血和肝组织来源的数据计算基因表达的变异预测分数，并评估其与VTE的相关性。对与新的VTE位点相关的性状进行孟德尔随机化分析。

最终，研究人员从GWAS Meta分析中确定了34个VTE风险的独立遗传信号，其中14个是新发现的。这包括11个新的相关的遗传位点(C1orf198、PLEK、OSMR-AS1、NUGGC/SCARA5、GRK5、MPHOSPH9、ARID4A、PLCG2、SMG6、EIF5A、STX10)，其中6个在3个已知基因中重复出现，3个为新发现的独立信号。

此外，TWAS还从全血和肝脏中发现了5个额外的基因表达水平在患者中存在差异，且不同于对照组的遗传位点(全血：SH2B3、SPSB1、RP11-747H7.3、RP4-737E23.2；肝脏：ERAP1)。在部分GWAS位点上，研究人员还找到了新的和已知区域的VTE相关信号与eQTL信号共定位的提示证据。随机化分析表明，血液特征可能是VTE的潜在危险因素之一。

综上所述，本研究确定了16个新的VTE易感位点；其中部分位点的关联信号可能是通过临近基因的表达介导的。

原始出处：

Sara Lindstrom， et al. Genomic and Transcriptomic Association Studies Identify 16 Novel Susceptibility Loci for Venous Thromboembolism. Blood 2019 ：blood.2019000435； doi： https：//doi.org/10.1182/blood.2019000435

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2019-11-09 fusion

#静脉#

35 0
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2020-04-13 xue8602

#静脉血#

34 0
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2020-06-22 vera_1203

#新发现#

41 0
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2020-04-19 zxl729

#易感位点#

47 0
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2019-08-22 最帅小男护

怎么说呢

107 0
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2019-08-20 Midas

命运一说更是迷人

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