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Rare Variants in Primary Immunodeficiency Genes and Their Functional Partners in Severe COVID-19

Authors :
Maryam B. Khadzhieva
Dmitry S. Kolobkov
Darya A. Kashatnikova
Alesya S. Gracheva
Ivan V. Redkin
Artem N. Kuzovlev
Lyubov E. Salnikova
Source :
Biomolecules, Vol 13, Iss 9, p 1380 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

The development of severe COVID-19, which is a complex multisystem disease, is thought to be associated with many genes whose action is modulated by numerous environmental and genetic factors. In this study, we focused on the ideas of the omnigenic model of heritability of complex traits, which assumes that a small number of core genes and a large pool of peripheral genes expressed in disease-relevant tissues contribute to the genetics of complex traits through interconnected networks. We hypothesized that primary immunodeficiency disease (PID) genes may be considered as core genes in severe COVID-19, and their functional partners (FPs) from protein–protein interaction networks may be considered as peripheral near-core genes. We used whole-exome sequencing data from patients aged ≤ 45 years with severe (n = 9) and non-severe COVID-19 (n = 11), and assessed the cumulative contribution of rare high-impact variants to disease severity. In patients with severe COVID-19, an excess of rare high-impact variants was observed at the whole-exome level, but maximal association signals were detected for PID + FP gene subsets among the genes intolerant to LoF variants, haploinsufficient and essential. Our exploratory study may serve as a model for new directions in the research of host genetics in severe COVID-19.

Details

Language :
English
ISSN :
2218273X
Volume :
13
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
edsdoj.b0727a1864a4da29f46b2640cb60311
Document Type :
article
Full Text :
https://doi.org/10.3390/biom13091380