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泰国人群中 COVID-19 易感性和疾病严重程度的宿主遗传因素。

Host genetic factors of COVID-19 susceptibility and disease severity in a Thai population.

机构信息

Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Department of Pathology, Faculty of Medicine, Srinakharinwirot University, Nakornnayok, Thailand.

出版信息

J Hum Genet. 2022 May;67(5):295-301. doi: 10.1038/s10038-021-01009-6. Epub 2022 Jan 11.

Abstract

Host genetic factors have been shown to play a role in SARs-CoV-2 infection in diverse populations. However, the genetic landscape differs among various ethnicities; therefore, we explored the host genetic factors associated with COVID-19 disease susceptivity and disease severity in a Thai population. We recruited and genotyped 212 unrelated COVID-19 Thai patients and 36 controls using Axiom Human Genotyping SARs-COV-2 array, including 847,384 single nucleotide polymorphisms related to SARs-COV-2 pathogenesis, immune response, and related comorbidity No SNPs passed the genome-wide significance threshold of p value <1 × 10. However, with a threshold of p value <1 × 10, a locus on chromosome 5q32 was found to have a suggestive association with COVID-19 disease susceptibility (p value 6.9 × 10; Q-Q plot λ = 0.805, odds ratio 0.02). Notably, IL17B is a gene located in this linkage disequilibrium block and is previously shown to play a part in inflammation and pneumonia. Additionally, a suggestive locus on chromosome 12q22, harboring EEA1 and LOC643339, was associated with COVID-19 disease severity (p value 1.3 × 10 - 4.4 × 10, Q-Q plot λ = 0.997, odds ratio 0.28-0.31). EEA1 is involved in viral entry into cells, while LOC643339 is a long non-coding RNA. In summary, our study suggested loci on chromosomes 5q32 and 12q22 to be linked to COVID-19 disease susceptibility and disease severity, respectively. The small sample size of this study may lessen the likelihood that the association found is real, but it could still be true. Further study with a larger cohort is required to confirm these findings.

摘要

宿主遗传因素已被证明在不同人群的 SARS-CoV-2 感染中发挥作用。然而,不同种族的遗传背景存在差异;因此,我们在泰国人群中探索了与 COVID-19 疾病易感性和疾病严重程度相关的宿主遗传因素。我们使用 Axiom Human Genotyping SARS-COV-2 阵列招募并基因分型了 212 名无关的 COVID-19 泰国患者和 36 名对照,包括与 SARS-COV-2 发病机制、免疫反应和相关合并症相关的 847,384 个单核苷酸多态性。没有 SNP 通过基因组范围显著阈值的 p 值<1×10。然而,在 p 值<1×10 的阈值下,发现染色体 5q32 上的一个位点与 COVID-19 疾病易感性具有提示性关联(p 值 6.9×10;Q-Q 图 λ=0.805,优势比 0.02)。值得注意的是,IL17B 是位于该连锁不平衡块中的一个基因,先前被证明在炎症和肺炎中起作用。此外,染色体 12q22 上的一个提示性位点,包含 EEA1 和 LOC643339,与 COVID-19 疾病严重程度相关(p 值 1.3×10-4.4×10,Q-Q 图 λ=0.997,优势比 0.28-0.31)。EEA1 参与病毒进入细胞,而 LOC643339 是一种长非编码 RNA。总之,我们的研究表明染色体 5q32 和 12q22 上的位点分别与 COVID-19 疾病易感性和疾病严重程度相关。这项研究的小样本量可能降低了所发现的关联是真实的可能性,但它仍然可能是真实的。需要更大的队列研究来证实这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce9f/8748005/ed56e06ca0a2/10038_2021_1009_Fig1_HTML.jpg

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