Laboratório de Genetica e Cardiologia Molecular, Instituto do Coracao (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, 05403-900, Brazil.
Genetics Department, Harvard Medical School, Boston, 02115, USA.
Hum Mol Genet. 2022 Sep 10;31(18):3021-3031. doi: 10.1093/hmg/ddac045.
The coronavirus disease 2019 (COVID-19) pandemic has changed the paradigms for disease surveillance and rapid deployment of scientific-based evidence for understanding disease biology, susceptibility and treatment. We have organized a large-scale genome-wide association study (GWAS) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals in Sao Paulo, Brazil, one of the most affected areas of the pandemic in the country, itself one of the most affected in the world. Here, we present the results of the initial analysis in the first 5233 participants of the BRACOVID study. We have conducted a GWAS for COVID-19 hospitalization enrolling 3533 cases (hospitalized COVID-19 participants) and 1700 controls (non-hospitalized COVID-19 participants). Models were adjusted by age, sex and the 4 first principal components. A meta-analysis was also conducted merging BRACOVID hospitalization data with the Human Genetic Initiative (HGI) Consortia results. BRACOVID results validated most loci previously identified in the HGI meta-analysis. In addition, no significant heterogeneity according to ancestral group within the Brazilian population was observed for the two most important COVID-19 severity associated loci: 3p21.31 and Chr21 near IFNAR2. Using only data provided by BRACOVID, a new genome-wide significant locus was identified on Chr1 near the genes DSTYK and RBBP5. The associated haplotype has also been previously associated with a number of blood cell related traits and might play a role in modulating the immune response in COVID-19 cases.
2019 年冠状病毒病（COVID-19）大流行改变了疾病监测和快速部署基于科学证据以了解疾病生物学、易感性和治疗方法的范式。我们在巴西圣保罗组织了一项针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染个体的大规模全基因组关联研究（GWAS），该城市是该国受疫情影响最严重的地区之一，也是世界上受疫情影响最严重的地区之一。在这里，我们介绍 BRACOVID 研究中前 5233 名参与者的初步分析结果。我们对 COVID-19 住院患者进行了 GWAS 研究，共纳入 3533 例病例（COVID-19 住院患者）和 1700 例对照（COVID-19 非住院患者）。模型调整了年龄、性别和前四个主要成分。还对 BRACOVID 住院数据与人类遗传倡议（HGI）协会的结果进行了合并的荟萃分析。BRACOVID 结果验证了 HGI 荟萃分析中先前确定的大多数基因座。此外，在巴西人群中，两个与 COVID-19 严重程度最相关的基因座：3p21.31 和 Chr21 附近 IFNAR2 没有观察到按祖先群体划分的显著异质性。仅使用 BRACOVID 提供的数据，在 Chr1 附近 DSTYK 和 RBBP5 基因附近发现了一个新的全基因组显著基因座。相关的单倍型也与许多血细胞相关特征有关，可能在调节 COVID-19 病例的免疫反应中发挥作用。
