Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity.

@article{Shelton2021TransancestryAR,
  title={Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity.},
  author={Janie F. Shelton and Anjali J. Shastri and Chelsea Ye and Catherine H. Weldon and Teresa Filshtein-Sonmez and Daniella Coker and Antony Symons and Jorge Esparza-Gordillo and Stella W. Aslibekyan and Adam Auton},
  journal={Nature genetics},
  year={2021}
}
COVID-19 presents with a wide range of severity, from asymptomatic in some individuals to fatal in others. Based on a study of 1,051,032 23andMe research participants, we report genetic and nongenetic associations with testing positive for SARS-CoV-2, respiratory symptoms and hospitalization. Using trans-ancestry genome-wide association studies, we identified a strong association between blood type and COVID-19 diagnosis, as well as a gene-rich locus on chromosome 3p21.31 that is more strongly… 
Expanded COVID-19 phenotype definitions reveal distinct patterns of genetic association and protective effects.
TLDR
It is concluded that continued large-scale ascertainment of deep CO VID-19 phenotype data would likely represent a boon for COVID-19 therapeutic target identification and suggest that three of the four 'expanded' COvid-19 phenotypes have enhanced power to capture protective genetic associations relative to the previously studied phenotypes.
Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population
TLDR
A genome-wide association study on 284 confirmed COVID-19 patients and controls and extrapolation of the identified HLA from the cohort to the worldwide population revealed notable correlations, which may provide new insights into the pathogenesis and clinical treatment of the disease.
Trans-ethnic genome-wide association study of severe COVID-19
TLDR
Findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.
A genome-wide association study of COVID-19 related hospitalization in Spain reveals genetic disparities among sexes
TLDR
Less SNP-heritability and larger heritability differences by age (<60/[≥]60 years) among males than females among females and inbreeding depression was associated with COVID-19 hospitalization and severity, and the effect was stronger among older males.
New susceptibility loci for severe COVID-19 by detailed GWAS analysis in European populations
TLDR
An extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany, as well as hypothesis-driven targeted analysis of the human leukocyte antigen (HLA) region and chromosome Y haplotypes are described.
Genetic risk factors associated with SARS-CoV-2 susceptibility in multiethnic populations
TLDR
A genome-wide association study of SARS-CoV-2 susceptibility in a multiethnic set of three populations (European, African, and South Asian) from a UK BioBank clinical and genomic dataset is conducted.
Genomic and Ancestral Variation Underlies the Severity of COVID-19 Clinical Manifestation in Individuals of European Descent
TLDR
The ancestry analysis revealed that the asymptomatic COVID-19 patients possess discernibly higher proportions of the Ancestral North Eurasian and Eastern Hunter-Gatherer ancestry, while severely symptomatic patients have higher fractions of WHG and lower ANE/EHG ancestral components, thereby delineating the likely ancestral differences between the two groups.
Host genetic factors determining COVID-19 susceptibility and severity
...
...

References

SHOWING 1-10 OF 30 REFERENCES
Associations between blood type and COVID-19 infection, intubation, and death
TLDR
Assessment of the association between ABO and Rh blood types and infection, intubation, and death in SARS-CoV-2 finds slightly increased infection prevalence among non-O types and estimates Rh-negative blood type to have a protective effect for all three outcomes.
Longitudinal analyses reveal immunological misfiring in severe COVID-19
TLDR
A longitudinal analysis of immune responses in patients with moderate or severe COVID-19 identifies a maladapted immune response profile linked to severe disease, as well as early immune signatures that correlate with divergent disease trajectories.
Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania
TLDR
A genome-wide association study of host resistance to severe Plasmodium falciparum malaria in over 17,000 individuals from 11 malaria- endemic countries will provide a major building block for future research on the genetic determinants of disease in these diverse human populations.
Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections
TLDR
Fine-mapping analysis is applied to dissect associations in the human leukocyte antigen region, which suggests important roles of specific amino acid polymorphisms in the antigen-binding clefts, an important step toward dissecting the host genetic architecture of response to common infections.
Factors associated with COVID-19-related death using OpenSAFELY
TLDR
A range of clinical factors associated with COVID-19-related death is quantified in one of the largest cohort studies on this topic so far and includes people of white ethnicity, Black and South Asian people were at higher risk, even after adjustment for other factors.
Viral and host factors related to the clinical outcome of COVID-19
TLDR
Clinical data from 326 cases suggest that T cell depletion and cytokine bursts are associated with a worse prognosis, and genomic sequences from 112 patients with confirmed SARS-CoV-2 virus showed two clades with similar virulence and clinical outcome.
Bayesian refinement of association signals for 14 loci in 3 common diseases
TLDR
Very few SNPs in the authors' credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases, and show the value of more detailed mapping to target sequences for functional studies.
Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications
TLDR
High-dimensional flow cytometry of hospitalized COVID-19 patients found three prominent and distinct immunotypes that are related to disease severity and clinical parameters, and a compendium of immune cell information and roadmaps for potential therapeutic interventions is provided.
The ubiquity of pleiotropy in human disease
TLDR
It is becoming evident that pleiotropy is a common, if not ubiquitous, phenomenon and has implications in understanding disease etiologies, potentially common biology underlying even disparate diseases, and in elucidating the genotype–phenotype map.
...
...