A genome-wide association study of COVID-19 related hospitalization in Spain reveals genetic disparities among sexes

Carracedo, Ángel

doi:10.1101/2021.11.24.21266741

Cited by 3 publications

(2 citation statements)

References 78 publications

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“…Male sex is one of the most impactful epidemiological risk factors for hospitalization and severe respiratory syndrome due to COVID-19, but initially large-scale genetic studies did not report sex-specific effects for infection susceptibility or severe disease. However, some reports of sex-specific effects are starting to emerge for loci containing immune-related genes 34 , 92 . Moreover, the rare variants in the chromosome X gene TLR7 affect males and are associated with severe COVID-19 outcomes 93 .…”

Section: Genetic Findingsmentioning

confidence: 99%

The human genetic epidemiology of COVID-19

2022

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Human genetics can inform the biology and epidemiology of coronavirus disease 2019 (COVID-19) by pinpointing causal mechanisms that explain why some individuals become more severely affected by the disease upon infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Large-scale genetic association studies, encompassing both rare and common genetic variants, have used different study designs and multiple disease phenotype definitions to identify several genomic regions associated with COVID-19. Along with a multitude of follow-up studies, these findings have increased our understanding of disease aetiology and provided routes for management of COVID-19. Important emergent opportunities include the clinical translatability of genetic risk prediction, the repurposing of existing drugs, exploration of variable host effects of different viral strains, study of inter-individual variability in vaccination response and understanding the long-term consequences of SARS-CoV-2 infection. Beyond the current pandemic, these transferrable opportunities are likely to affect the study of many infectious diseases.

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Section: Genetic Findingsmentioning

confidence: 99%

The human genetic epidemiology of COVID-19

2022

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“…1;5 Further genetic discoveries may identify additional therapeutic targets to modulate severe disease. 6 In this new data release from the GenOMICC (Genetics Of Mortality in Critical Care) study we include new microarray genotyping data from additional critically-ill cases in the UK and Brazil, together with cohorts of severe Covid-19 from the ISARIC4C 7 and SCOURGE 8 studies, and meta-analysis with previously-reported data. We find an additional 14 new genetic associations.…”

mentioning

confidence: 99%

GWAS and meta-analysis identifies multiple new genetic mechanisms underlying severe Covid-19

Pairo-Castineira

Rawlik

Klarić

et al. 2022

Preprint

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Pulmonary inflammation drives critical illness in Covid-19, creating a clinically homogeneous extreme phenotype, which we have previously shown to be highly efficient for discovery of genetic associations. Despite the advanced stage of illness, we have found that immunomodulatory therapies have strong beneficial effects in this group. Further genetic discoveries may identify additional therapeutic targets to modulate severe disease. In this new data release from the GenOMICC (Genetics Of Mortality in Critical Care) study we include new microarray genotyping data from additional critically-ill cases in the UK and Brazil, together with cohorts of severe Covid-19 from the ISARIC4C and SCOURGE studies, and meta-analysis with previously-reported data. We find an additional \numconvincingnew new genetic associations. Many are in potentially druggable targets, in inflammatory signalling (JAK1, PDE4A), monocyte-macrophage differentiation (CSF2), immunometabolism (SLC2A5, AK5), and host factors required for viral entry and replication (TMPRSS2, RAB2A). As with our previous work, these results provide tractable therapeutic targets for modulation of harmful host-mediated inflammation in Covid-19.

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Exome-wide association study for replication of rare variants affecting the severity of COVID-19 in the Russian population

Apalko,

Nostaeva,

Shimansky

et al. 2024

Genes & Cells

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BACKGROUND: Human genetics is one of the factors determining the severity of COVID-19 disease. Previously, a large-scale whole-genome association study of the COVID-19 HG project (COVID-19 Host Genetics Initiative, 2021) investigated the association of genetic variants at multiple loci with COVID-19 severity. The genetic variants that have the greatest impact on COVID-19 severity are expected to have a low frequency in the population. Therefore, the study of rare variants may provide additional insights into the pathogenesis of the disease and thus help in the development of prevention and treatment options. AIM: The aim is to perform a replication analysis in search of genes with enrichment for rare genetic variants in relation to the severity of COVID-19 disease. METHODS: In this study, the clinical exome of a Russian cohort of patients was sequenced based on the St. Petersburg State Budgetary Institution "City Hospital No. 40" and St. Petersburg State University. The study used biomaterial from patients hospitalised at "City Hospital No. 40" with a diagnosis of COVID-19 and healthy individuals included in the population control group. The severity of the course of COVID-19 was determined according to the results of lung computed tomography. The list of genes for subsequent replication was generated by a literature review. Replication analysis of genes associated with COVID-19 severity was performed using burden test methods. RESULTS: In total, 701 clinical exomes were sequenced: 263 severe COVID-19 and 438 healthy individuals. A literature review identified 18 genes associated with severe COVID-19 that were included in the replication analysis. The replication analysis did not identify any genes whose association with severe COVID-19 was confirmed in the study cohort. CONCLUSION: Replication analysis did not identify any genes for which a significant association between functional variant enrichment and COVID-19 severity was found. However, the results demonstrated that the direction of the correlation was consistent with findings from previous studies. The small size of the sample analysed is an obvious limitation of our study. Expanding the study cohort would increase the power of the tests and allow us to detect additional rare variants that influence the severity of COVID-19 progression

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A genome-wide association study of COVID-19 related hospitalization in Spain reveals genetic disparities among sexes

Cited by 3 publications

References 78 publications

The human genetic epidemiology of COVID-19

The human genetic epidemiology of COVID-19

GWAS and meta-analysis identifies multiple new genetic mechanisms underlying severe Covid-19

Exome-wide association study for replication of rare variants affecting the severity of COVID-19 in the Russian population

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