The human genetic epidemiology of COVID-19

Niemi, Mari; Daly, Mark J.; Ganna, Andrea

doi:10.1038/s41576-022-00478-5

Cited by 118 publications

(121 citation statements)

References 140 publications

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“…In COVID-19, a PRS could estimate the individual risk for disease susceptibility or severity based on common and rare variants that are found to be enriched in GWAS studies. Although some studies have already attempted to model the PRS for COVID-19, more research is required to build a PRS model that is robust and can be applied to patients with different genetic and medical backgrounds [41,50,142,143].…”

Section: Diagnostic Sequencingmentioning

confidence: 99%

Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19

et al. 2022

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Since the start of the coronavirus disease 2019 (COVID-19) pandemic, important insights have been gained into virus biology and the host factors that modulate the human immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 displays a highly variable clinical picture that ranges from asymptomatic disease to lethal pneumonia. Apart from well-established general risk factors such as advanced age, male sex and chronic comorbidities, differences in host genetics have been shown to influence the individual predisposition to develop severe manifestations of COVID-19. These differences range from common susceptibility loci to rare genetic variants with strongly predisposing effects, or proven pathogenic variants that lead to known or novel inborn errors of immunity (IEI), which constitute a growing group of heterogeneous Mendelian disorders with increased susceptibility to infectious disease, auto-inflammation, auto-immunity, allergy or malignancies. The current genetic findings point towards a convergence of common and rare genetic variants that impact the interferon signalling pathways in patients with severe or critical COVID-19. Monogenic risk factors that impact IFN-I signalling have an expected prevalence between 1 and 5% in young, previously healthy individuals (<60 years of age) with critical COVID-19. The identification of these IEI such as X-linked TLR7 deficiency indicates a possibility for targeted genetic screening and personalized clinical management. This review aims to provide an overview of our current understanding of the host genetic factors that predispose to severe manifestations of COVID-19 and focuses on rare variants in IFN-I signalling genes and their potential clinical implications.

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Section: Diagnostic Sequencingmentioning

confidence: 99%

Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19

et al. 2022

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“…From the beginning of the pandemic, MR has played a critical role in providing evidence of modifiable risk factors for COVID-19 2,11,12 . Furthermore, multiple MR studies identified potential therapeutic targets for COVID-19, including OAS1, ABO, IFNAR2, IL-6, ELF5, and FAS [12][13][14][15][16][17][18] . Indeed, some MR findings have been validated by randomized controlled trials, demonstrating the utility of MR [19][20][21][22][23][24] .…”

Section: Introductionmentioning

confidence: 99%

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity

Yoshiji

Butler‐Laporte

et al. 2022

Preprint

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Obesity is a major risk factor for COVID-19 severity; however, the underlying mechanism is not fully understood. Considering that obesity influences the human plasma proteome, we sought to identify circulating proteins mediating the effects of obesity on COVID-19 severity. We first screened 4,907 plasma proteins to identify proteins influenced by body mass index (BMI) using Mendelian randomization (MR). This yielded 1,216 proteins, whose effects on COVID-19 severity were assessed, again using MR. This two-step approach identified nephronectin (NPNT), for which a one standard deviation increase was associated with severe COVID-19 (odds ratio = 1.71, 95% CI: 1.45–2.02, P = 1.63 × 10-10). Colocalization analyses indicated that an NPNT splice isoform drove this effect. Overall, NPNT mediates 3.7% of the total effect of BMI on severe COVID-19. Finally, we found that decreasing body fat mass and increasing fat-free mass can lower NPNT levels and thus may improve COVID-19 outcomes. These findings provide actionable insights into how obesity influences COVID-19 severity.

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“…Several demographics, clinical, phenotype or even genetic variables have been described to be associated with the progression of COVID-19 and multisystemic manifestations [14]. Immunological response to the virus can also involve hepatic, gastrointestinal, cardiac, renal, neurological and hematological complications [15].…”

Section: Introductionmentioning

confidence: 99%

Hematological- and Immunological-Related Biomarkers to Characterize Patients with COVID-19 from Other Viral Respiratory Diseases

Suárez-Del-Villar-Carrero

Martínez-Urbistondo

Cuevas-Sierra

et al. 2022

JCM

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COVID-19 has overloaded health system worldwide; thus, it demanded a triage method for an efficient and early discrimination of patients with COVID-19. The objective of this research was to perform a model based on commonly requested hematological variables for an early featuring of patients with COVID-19 form other viral pneumonia. This investigation enrolled 951 patients (mean of age 68 and 56% of male) who underwent a PCR test for respiratory viruses between January 2019 and January 2020, and those who underwent a PCR test for detection of SARS-CoV-2 between February 2020 and October 2020. A comparative analysis of the population according to PCR tests and logistic regression model was performed. A total of 10 variables were found for the characterization of COVID-19: age, sex, anemia, immunosuppression, C-reactive protein, chronic obstructive pulmonary disease, cardiorespiratory disease, metastasis, leukocytes and monocytes. The ROC curve revealed a sensitivity and specificity of 75%. A deep analysis showed low levels of leukocytes in COVID-19-positive patients, which could be used as a primary outcome of COVID-19 detection. In conclusion, this investigation found that commonly requested laboratory variables are able to help physicians to distinguish COVID-19 and perform a quick stratification of patients into different prognostic categories.

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The human genetic epidemiology of COVID-19

Cited by 118 publications

References 140 publications

Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19

Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity

Hematological- and Immunological-Related Biomarkers to Characterize Patients with COVID-19 from Other Viral Respiratory Diseases

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