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全基因组跨性状分析和孟德尔随机化揭示了 COVID-19 和静脉血栓栓塞之间存在共同的遗传病因和因果关系。

Genome-wide cross-trait analysis and Mendelian randomization reveal a shared genetic etiology and causality between COVID-19 and venous thromboembolism.

机构信息

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.

Department of Statistics and Actuarial Science, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.

出版信息

Commun Biol. 2023 Apr 21;6(1):441. doi: 10.1038/s42003-023-04805-2.

DOI:10.1038/s42003-023-04805-2
PMID:37085521
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10120502/
Abstract

Venous thromboembolism occurs in up to one-third of patients with COVID-19. Venous thromboembolism and COVID-19 may share a common genetic architecture, which has not been clarified. To fill this gap, we leverage summary-level genetic data from the latest COVID-19 host genetics consortium and UK Biobank and examine the shared genetic etiology and causal relationship between COVID-19 and venous thromboembolism. The cross-trait and co-localization analyses identify 2, 3, and 4 shared loci between venous thromboembolism and severe COVID-19, COVID-19 hospitalization, SARS-CoV-2 infection respectively, which are mapped to ABO, ADAMTS13, FUT2 genes involved in coagulation functions. Enrichment analysis supports shared biological processes between COVID-19 and venous thromboembolism related to coagulation and immunity. Bi-directional Mendelian randomization suggests that venous thromboembolism was associated with higher risk of three COVID-19 traits, and SARS-CoV-2 infection was associated with a higher risk of venous thromboembolism. Our study provides timely evidence for the genetic etiology between COVID-19 and venous thromboembolism (VTE). Our findings contribute to the understanding of COVID-19 and VTE etiology and provide insights into the prevention and comorbidity management of COVID-19.

摘要

静脉血栓栓塞症（VTE）在高达三分之一的 COVID-19 患者中发生。静脉血栓栓塞症和 COVID-19 可能具有共同的遗传结构，但尚未阐明。为了填补这一空白，我们利用来自最新 COVID-19 宿主遗传学联盟和英国生物银行的汇总水平遗传数据，研究 COVID-19 和 VTE 之间的共同遗传病因学和因果关系。跨特征和共定位分析在静脉血栓栓塞症和严重 COVID-19、COVID-19 住院、SARS-CoV-2 感染之间分别识别出 2、3 和 4 个共享位点，这些位点映射到涉及凝血功能的 ABO、ADAMTS13、FUT2 基因。富集分析支持 COVID-19 和静脉血栓栓塞症之间与凝血和免疫相关的共同生物学过程。双向 Mendelian 随机化表明，静脉血栓栓塞症与 COVID-19 的三种特征（严重程度、住院治疗、感染 SARS-CoV-2）的风险增加相关，而 SARS-CoV-2 感染与静脉血栓栓塞症的风险增加相关。我们的研究为 COVID-19 和 VTE 之间的遗传病因提供了及时的证据。我们的研究结果有助于理解 COVID-19 和 VTE 的病因，并为 COVID-19 的预防和合并症管理提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/7d13faea40cb/42003_2023_4805_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/e15aa0052e23/42003_2023_4805_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/7319d9266768/42003_2023_4805_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/b02004939b90/42003_2023_4805_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/7d13faea40cb/42003_2023_4805_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/e15aa0052e23/42003_2023_4805_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/19b807792fdf/42003_2023_4805_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/79fb5394ca61/42003_2023_4805_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/7319d9266768/42003_2023_4805_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/b02004939b90/42003_2023_4805_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa2/10121714/7d13faea40cb/42003_2023_4805_Fig6_HTML.jpg

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