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单基因和多基因全基因组扫描为静脉血栓栓塞提供新的遗传风险修饰因子。

Single- and Multimarker Genome-Wide Scans Evidence Novel Genetic Risk Modifiers for Venous Thromboembolism.

机构信息

Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany.

Department of Biochemistry, Genetic Epidemiology and Statistical Genetics, Maastricht University, Maastricht, The Netherlands.

出版信息

Thromb Haemost. 2021 Sep;121(9):1169-1180. doi: 10.1055/s-0041-1723988. Epub 2021 Feb 16.

Abstract

Previous genome-wide association studies (GWASs) have established several susceptibility genes for venous thromboembolism (VTE) and suggested many others. However, a large proportion of the genetic variance in VTE remains unexplained. Here, we report genome-wide single- and multimarker as well as gene-level associations with VTE in 964 cases and 899 healthy controls of European ancestry. We report 19 loci at the genome-wide level of association ( ≤ 5 × 10). Our results add to the strong support for the association of genetic variants in , , and with VTE, and identify several loci that have not been previously associated with VTE. Altogether, our novel findings suggest that 20 susceptibility genes for VTE were newly discovered by our study. These genes may impact the production and prothrombotic functions of platelets, endothelial cells, and white and red blood cells. Moreover, the majority of these genes have been previously associated with cardiovascular diseases and/or risk factors for VTE. Future studies are warranted to validate our findings and to investigate the shared genetic architecture with susceptibility factors for other cardiovascular diseases impacting VTE risk.

摘要

先前的全基因组关联研究(GWAS)已经确定了静脉血栓栓塞症(VTE)的几个易感基因,并提示了许多其他基因。然而,VTE 的遗传变异很大一部分仍未得到解释。在这里,我们报告了在 964 例欧洲血统的静脉血栓栓塞症患者和 899 例健康对照者中,全基因组单标记和多标记以及基因水平与静脉血栓栓塞症的关联。我们报告了在全基因组关联水平上的 19 个位点(≤5×10)。我们的研究结果进一步支持了遗传变异与静脉血栓栓塞症的关联,在 、 和 中发现了几个以前与静脉血栓栓塞症无关的位点。总的来说,我们的新发现表明,我们的研究新发现了 20 个静脉血栓栓塞症的易感基因。这些基因可能影响血小板、内皮细胞以及白细胞和红细胞的生成和促血栓形成功能。此外,这些基因中的大多数以前与心血管疾病和/或静脉血栓栓塞症的风险因素有关。未来的研究需要验证我们的发现,并研究与影响静脉血栓栓塞症风险的其他心血管疾病易感性因素的共同遗传结构。

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