Genetic risk factors and COVID-19 severity in Brazil: results from BRACOVID study

Abstract

The 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 in 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.

Host genetic determinants of COVID‐19 susceptibility and severity: A systematic review and meta‐analysis

“…A total of 17 eligible studies were included for the analysis. Of the included studies, 15 employed a case‐control study design and performed GWAS in a total of 96,817 COVID‐19 cases and 6,414,916 negative controls 3,4,6–8,10,11,21–28 . Five studies estimated the narrow‐sense heritability of COVID‐19 infection and severity based on GWAS summary statistics 3,7,8,20 and Monte‐Carlo estimation from AncestryDNA Survey Data 29 .…”

“…Eligibility (full-text review) was performed on the remaining 42 reports; 25 articles were excluded based on predefined inclusion criteria. Finally, a total of 17 studies were included for a systematic review and meta-analysis of COVID-19 susceptibility and severity 3,4,[6][7][8]10,11,[20][21][22][23][24][25][26][27][28][29] (Figure 1).…”

“…Of the included studies, 15 employed a case-control study design and performed GWAS in a total of 96,817 COVID-19 cases and 6,414,916 negative controls. 3,4,[6][7][8]10,11,[21][22][23][24][25][26][27][28] Five studies estimated the narrow-sense heritability of COVID-19 infection and severity based on GWAS summary statistics 3,7,8,20 and Monte-Carlo estimation from AncestryDNA Survey Data. 29 Of the included studies, the COVID-19 Host Genetics Initiative (COVID-19 HGI) is the largest consortium, including 49,562 cases and 2,070,709 controls from 46 GWAS in 54 countries.…”

Interactions between genetic and lifestyle factors on cardiometabolic disease-related outcomes in Latin American and Caribbean populations: A systematic review

“…Moreover, no studies have examined the impact of rural and urban environments on the genetic predisposition to cardiometabolic diseases, highlighting a gap in knowledge in LACP. The higher number of nutrigenetic studies in Brazil compared to the other countries could be attributed to several factors including existing data on genetic studies (176)(177)(178)(179)(180)(181), GWAS done mainly in Brazil (182)(183)(184), increased awareness on nutrigenetics in Brazil or more research facilities available in Brazil compared to other LACP. Future gene-lifestyle interaction studies will need to replicate primary research of already studied genetic variants to enable comparison, and to explore the interactions between genetic and other lifestyle factors such as those conditioned by socioeconomic factors and the built environment.…”

Effect of Age, Sex, and COVID-19 Vaccination History on All-Cause Mortality: Unexpected Outcomes in a Complex Biological and Social System

“…There is now increasing evidence that the risk of COVID-19 morbidity and mortality has a strong genetic basis centered around chromosome 3 mutations inherited from Neanderthals, hence, higher risk among various people groups, and certain blood groups [130][131][132][133][134][135][136][137][138][139]. Nakanishi et al [131] showed that chromosome 3 rs10490770 risk allele carriers had a 40% increased risk of all-cause mortality , 110% increased risk of severe respiratory failure, +70% venous thromboembolism, and +50% hepatic injury.…”