Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populations DOI Creative Commons
Tisham De, Lachlan Coin, Jethro Herberg

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 16, 2025

Abstract Copy number variants (CNVs) are an important class of genomic variation known to be for human physiology and diseases. Here we present genome-wide metabolomic signatures CNVs in two Finnish cohorts—The Northern Finland Birth Cohort 1966 (NFBC 1966) NFBC 1986. We have analysed reported over 9,300 individuals characterised their dosage effect (CNV-metabolomic QTL) on 228 plasma lipoproteins metabolites. reference (normal physiology) up ~ 2.6 million COVID-19 GWAS results from the National Institutes Health (NIH) GRASP database, including outcomes related death, severity, hospitalisation. Furthermore, by analysing exemplar genes severity namely LZTFL1 OAS1, here additional candidate biology, (1) NFIX, a gene viral (adenovirus) replication hematopoietic stem cells (2) ACSL1, sepsis bacterial inflammation. Based our current literature hypothesise that charge imbalance across cellular membrane between cations (Fe 2+ , Mg etc.) anions (e.g. ROS, hydroxide ion Fenton reactions, superoxide etc.), iron trafficking within different cell types e.g., macrophages (3) systemic oxidative stress response lipid peroxidation mediated inflammation), together could relevance severe cases. To conclude, unique atlas univariate multivariate (~ 7.2 signatures) with deep annotations various multi-omics data sets provide knowledge base metabolism

Language: Английский

SARS-CoV-2 variant biology: immune escape, transmission and fitness DOI Creative Commons
Alessandro M. Carabelli, Thomas P. Peacock, Lucy Thorne

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Language: Английский

Citations

989
Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors DOI Creative Commons
Levente Zsichla, Viktor Müller

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 175 - 175

Published: Jan. 7, 2023

The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease death. Understanding the risk factors is relevant both in setting at epidemiological level. Here, we provide an overview host, viral environmental that have been shown or (in some cases) hypothesized be associated with outcomes. considered detail include age frailty, genetic polymorphisms, biological sex (and pregnancy), co- superinfections, non-communicable comorbidities, immunological history, microbiota, lifestyle patient; variation infecting dose; socioeconomic factors; air pollution. For each category, compile (sometimes conflicting) evidence for association factor outcomes (including strength effect) outline possible action mechanisms. We also discuss complex interactions between various factors.

Language: Английский

Citations

71
Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity DOI Open Access
Satoshi Yoshiji, Guillaume Butler‐Laporte, Tianyuan Lu

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(2), P. 248 - 264

Published: Feb. 20, 2023

Language: Английский

Citations

58
Common genetic factors among autoimmune diseases DOI
Adil Harroud, David A. Hafler

Science, Journal Year: 2023, Volume and Issue: 380(6644), P. 485 - 490

Published: May 4, 2023

Autoimmune diseases display a high degree of comorbidity within individuals and families, suggesting shared risk factors. Over the past 15 years, genome-wide association studies have established polygenic basis these common conditions revealed widespread sharing genetic effects, indicative immunopathology. Despite ongoing challenges in determining precise genes molecular consequences variants, functional experiments integration with multimodal genomic data are providing valuable insights into key immune cells pathways driving diseases, potential therapeutic implications. Moreover, ancient populations shedding light on contribution pathogen-driven selection pressures to increased prevalence autoimmune disease. This Review summarizes current understanding disease genetics, including mechanisms, evolutionary origins.

Language: Английский

Citations

47
Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19 DOI Creative Commons
Caspar I. van der Made, Mihai G. Netea,

Frank L. van der Veerdonk

et al.

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: Aug. 19, 2022

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

Language: Английский

Citations

59
Genetic susceptibility to severe COVID-19 DOI Creative Commons
Claudio Cappadona, Valeria Rimoldi, Elvezia Maria Paraboschi

et al.

Infection Genetics and Evolution, Journal Year: 2023, Volume and Issue: 110, P. 105426 - 105426

Published: March 17, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of disease 2019 (COVID-19) pandemic. Clinical manifestations range from an asymptomatic condition to life-threatening events and death, with more severe courses being associated age, male sex, comorbidities. Besides these risk factors, intrinsic characteristics virus as well genetic factors host are expected account for COVID-19 clinical heterogeneity. Genetic studies have long been recognized fundamental identify biological mechanisms underlying congenital diseases, pinpoint genes/proteins responsible susceptibility different inherited conditions, highlight targets therapeutic relevance, suggest drug repurposing, even clarify causal relationships that make modifiable some environmental factors. Though usually take time be concluded and, above all, translate their discoveries patients' bedside, scientific community moved really fast deliver signals phenotypes. In this Review, besides a concise description symptomatology SARS-CoV-2 mechanism infection, we aimed recapitulate current literature in terms specifically associate increased severity disease.

Language: Английский

Citations

26
Genetic justification of COVID‐19 patient outcomes using DERGA, a novel data ensemble refinement greedy algorithm DOI Creative Commons
Panagiotis G. Asteris, Amir H. Gandomi, Danial Jahed Armaghani

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(4)

Published: Feb. 1, 2024

Abstract Complement inhibition has shown promise in various disorders, including COVID‐19. A prediction tool complement genetic variants is vital. This study aims to identify crucial complement‐related and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID‐19 patients hospitalized between April 2020 2021 at three referral centres were analysed using artificial intelligence‐based algorithm predict (ICU vs. non‐ICU admission). recently introduced alpha‐index identified the 30 most predictive variants. DERGA algorithm, which employs multiple classification algorithms, determined of these key variants, resulting 97% accuracy predicting outcome. Individual variations ranged 40 161 per patient, with 977 total detected. demonstrates utility ranking a substantial number approach enables implementation well‐established algorithms that effectively relevance outcomes high accuracy.

Language: Английский

Citations

13
The global clinical studies of long COVID DOI
Diego Ramonfaur, Nardeen Ayad,

Peter Hong Zhi Liu

et al.

International Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: 146, P. 107105 - 107105

Published: May 22, 2024

Language: Английский

Citations

8
Pathogenesis of viral infection DOI
Wenjing Zai, Zhenghong Yuan

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 2187 - 2207

Published: Jan. 1, 2024

Language: Английский

Citations

7
Type 2 diabetes and its genetic susceptibility are associated with increased severity and mortality of COVID-19 in UK Biobank DOI Creative Commons

A. Lee,

Ji-Eun Seo,

Seunghwan Park

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Jan. 24, 2024

Abstract Type 2 diabetes (T2D) is known as one of the important risk factors for severity and mortality COVID-19. Here, we evaluate impact T2D its genetic susceptibility on COVID-19, using 459,119 individuals in UK Biobank. Utilizing polygenic scores (PRS) T2D, identified a significant association between or PRS, COVID-19 severity. We further discovered efficacy vaccination pivotal role T2D-related genetics pathogenesis severe Moreover, found that with those high PRS group had significantly increased rate. also observed rate SARS-CoV-2-infected patients was approximately to 7 times higher than not infected, depending time infection. These findings emphasize potential estimating

Language: Английский

Citations

6