Laboratório de Biologia Integrativa, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Grupo de Pesquisa em Bioestatística e Epidemiologia molecular, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Rev Med Virol. 2022 Mar;32(2):e2283. doi: 10.1002/rmv.2283. Epub 2021 Aug 2.
Biomarker identification may provide strategic opportunities to understand disease pathophysiology, predict outcomes, improve human health, and reduce healthcare costs. The highly heterogeneous Covid-19 clinical manifestation suggests a complex interaction of several different human, viral and environmental factors. Here, we systematically reviewed genetic association studies evaluating Covid-19 severity or susceptibility to SARS-CoV-2 infection following PRISMA recommendations. Our research comprised papers published until December 31 , 2020, in PubMed and BioRXiv databases focusing on genetic association studies with Covid-19 prognosis or susceptibility. We found 20 eligible genetic association studies, of which 11 assessed Covid-19 outcome and 14 evaluated infection susceptibility (five analyzed both effects). Q-genie assessment indicated moderate quality. Five large-scale association studies (GWAS, whole-genome, or exome sequencing) were reported with no consistent replication to date. Promising hits were found on the 3p21.31 region and ABO locus. Candidate gene studies examined ACE1, ACE2, TMPRSS2, IFITM3, APOE, Furin, IFNL3, IFNL4, HLA, TNF-ɑ genes, and ABO system. The most evaluated single locus was the ABO, and the most sampled region was the HLA with three and five candidate gene studies, respectively. Meta-analysis could not be performed. Available data showed the need for further reports to replicate claimed associations.
生物标志物的识别可能提供战略机会，以了解疾病的病理生理学，预测结果，改善人类健康，并降低医疗保健成本。高度异质的新冠病毒临床症状表明，几种不同的人类、病毒和环境因素之间存在复杂的相互作用。在这里，我们系统地回顾了评估新冠病毒严重程度或对 SARS-CoV-2 感染易感性的遗传关联研究，这些研究符合 PRISMA 建议。我们的研究包括截至 2020 年 12 月 31 日在 PubMed 和 BioRXiv 数据库中发表的论文，这些论文主要关注与新冠病毒预后或易感性相关的遗传关联研究。我们发现了 20 项符合条件的遗传关联研究，其中 11 项评估了新冠病毒的结果，14 项评估了感染的易感性（5 项分析了这两种效果）。Q-genie 评估表明质量中等。目前还没有一致的重复报道五项大型关联研究（GWAS、全基因组或外显子测序）。在 3p21.31 区域和 ABO 基因座上发现了有希望的候选基因。候选基因研究检测了 ACE1、ACE2、TMPRSS2、IFITM3、APOE、Furin、IFNL3、IFNL4、HLA、TNF-ɑ 基因和 ABO 系统。评估最多的单基因座是 ABO，采样最多的区域是 HLA，分别有三个和五个候选基因研究。由于数据有限，无法进行荟萃分析。现有数据表明，需要进一步的报告来重复声称的关联。
