Regional European genetic ancestry predicts type I interferon level and risk of severe viral infection.

Autor:	Nln I; Division of Rheumatology, Department of Medicine, Hospital for Special Surgery, New York, NY, USA., Shum J; Department of Medicine, MarinHealth Medical Center, Kentfield, CA, USA., Ghodke-Puranik Y; Division of Rheumatology, Department of Medicine, Hospital for Special Surgery, New York, NY, USA., Tipon R; The New York Stem Cell Foundation, New York, NY, USA., Triese D; Division of Rheumatology, Mayo Clinic, Rochester, MN, USA., Amin S; Division of Rheumatology, Mayo Clinic, Rochester, MN, USA., Makol A; Division of Rheumatology, Mayo Clinic, Rochester, MN, USA., Osborn T; Division of Rheumatology, Mayo Clinic, Rochester, MN, USA., Chowdhary V; Division of Rheumatology, Yale University, New Haven, CT, USA., Thanarajasingam U; Division of Rheumatology, Mayo Clinic, Rochester, MN, USA., Muskardin TLW; Division of Rheumatology, Department of Medicine, Hospital for Special Surgery, New York, NY, USA., Oke V; Division of Rheumatology, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden., Gunnarsson I; Division of Rheumatology, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden., Zickert A; Division of Rheumatology, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden., Zervou MI; Laboratory of Molecular Medicine and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, Heraklion, Greece., Boumpas DT; Biomedical Research Foundation, Academy of Athens, Athens, Greece., Svenungsson E; Division of Rheumatology, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden., Goulielmos GN; Laboratory of Molecular Medicine and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, Heraklion, Greece., Niewold TB; Division of Rheumatology, Department of Medicine, Hospital for Special Surgery, New York, NY, USA.
Jazyk:	angličtina
Zdroj:	QJM : monthly journal of the Association of Physicians [QJM] 2024 Aug 01; Vol. 117 (8), pp. 581-588.
DOI:	10.1093/qjmed/hcae052
Abstrakt:	Background: Viral infection outcomes vary widely between individuals, ranging from mild symptoms to severe organ failure and death, and it is clear that host genetic factors play a role in this variability. Type I interferon (IFN) is a critical anti-viral cytokine, and we have previously noted differences in type I IFN levels between world populations. Methods: In this study, we investigate the interrelationship between regional European genetic ancestry, type I IFN levels and severe viral infection outcomes. Results: In cohorts of European ancestry lupus patients living in Europe, we noted higher IFN in the Northwestern populations as compared to Southeastern populations. In an independent cohort of European ancestry lupus patients from the USA with varying proportional regional European genetic admixture, we observed the same Northwest vs. Southeast European ancestry IFN gradient. We developed a model to predict type I IFN level based on regional European ancestry (Area under the curve (AUC) = 0.73, P = 6.1e-6). Examining large databases containing serious viral outcomes data, we found that lower predicted IFN in the corresponding European country was significantly correlated with increased viral infection fatality rate, including Coronavirus Disease 2019 (COVID-19), viral hepatitis and HIV [correlation coefficients: -0.79 (P = 4e-2), -0.94 (P = 6e-3) and -0.96 (P = 8e-2), respectively]. Conclusions: This association between predicted type I IFN level and viral outcome severity suggests a potential causal relationship, as greater intrinsic type I IFN is beneficial in host defense against viruses. Genetic testing could provide insight into individual and population level risk of fatality due to viruses prior to infection, across a wide range of viral pathogens. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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