The coronavirus pandemic 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) continues to be a major public health threat, especially in countries with low rates of vaccination. To inform public health measures it is crucial to comprehend the biological basis for COVID-19 severity and SARS-CoV-2. A new study has been published about the preprint server that is part of the COVID19 Host Genetics initiative.
Study: A revision to map the human genetic architecture in COVID-19. Image Credit: Studio.c/ Shutterstock
A new study
Researchers presented a thorough meta-analysis of the current study, and also added 10 genome-wide important loci. The GWAS meta-analysis covered up to 125,584 patients and more than 2.5 million controls (across 60 studies in 25 countries). The genes in the novel loci comprised SFTPD, MUC5B, and ACE2 that provided significant information regarding disease susceptibility and severity.
Researchers presented meta-analyses of 3 COVID-19 related types of phenotypes. The first one was for critically sick patients who required respiratory care in a hospital or died from the disease. It included 1,776,645 control cases and 9,376 cases. The second phenotype was those with moderate or severe COVID-19, defined as those who were who were hospitalized because of symptoms associated with the infection (25,027 cases and 2,836,272 controls). The last phenotype included all cases of SARS-CoV-2 infection regardless of symptoms. Researchers identified 23 genome-wide significant loci of which 20 were significant even after multiple corrections to tests to take into account the number of phenotypes that were examined.
Scientists discovered clear patterns of linkage with the different phenotypes at the genome-wide important loci. Based on the patterns of association between COVID-19 hospitalizations as well as SARS-CoV-2 reports of infection, they developed a Bayesian model that can categorize loci by using a Bayesian two-class Bayesian model. As susceptibility is associated with severity, it’s expected that loci are associated with severity. However, the genetic factors that only alter the course of illness are likely to be related to the severity of the disease only. Researchers identified seven genes that may influence the susceptibility to infection with SARS/CoV-2, and 16 loci that are significantly more likely to increase the risk of COVID-19 hospitalization.
A number of loci were found to have significant heterogeneous effects across different studies, and researchers were able to study whether these differences were caused by differences between continental ancestry groups. Only FOXP4 demonstrated a significant difference in effect across ancestries, which suggests that the factors that caused the heterogeneity between studies, rather than differences across ancestries.
Researchers identified potential causal genes and conducted a phenome-wide association analysis to better understand their biological processes. Numerous loci that play a role in the severity of COVID-19 were implicated in lung surfactant biology. The missense variant, rs721917.A>G (p.Met31Thr) found in SFTPD (10q22.3) was shown to increase hospitalization risk and was previously associated with increased risk of developing chronic obstructive lung disease. SFTPD plays an important role because it encodes the surfactant protein, which protects the lungs from inhaled microorganisms. Scientists have identified a second variant (rs35705950-G>T) that was protective against hospitalization. It was also found to improve the survival rate in idiopathic pulmonary fibrosis patients who carry this mutation.
In addition, rs190509934 t>C (located in bp downstream of ACE2) was associated with decreased susceptibility risk. Notably, rs190509934 was found to be ten times more prevalent in South Asians than Europeans which highlights the importance of diversity in discovery of variants. Recent research has revealed that the rs190509934T>C variant may lower the expression of ACE2. This could confer protection against SARS-CoV-2 infection. Another interesting finding was the existence of a causal relationship between genetic vulnerability to type II diabetes, SARS-CoV-2 infection and hospitalization.
In this study, researchers have presented meta-analyses of a variety of people from a variety of studies to understand better the biological basis of SARS-CoV-2 infection and disease severity. Researchers could examine whether COVID-19-related genetic variations had an impact on individuals from different ancestry groups by expanding genomic research. However, this was not the case, and the variation could be explained by the various research inclusion criteria regarding COVID-19 severity. These biological insights were vital because of the growth of the COVID-19 Host Genetic Initiative. These results demonstrated that increasing sample size and diversity is crucial to better understand COVID-19’s human genetic structure.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Content Source: https://www.news-medical.net/news/20211115/Updated-mapping-of-the-human-genetic-architecture-of-COVID-19.aspx