The landscape of host genetic factors involved in immune response to common viral infections.
Genome Med
; 12(1): 93, 2020 10 27.
Article
in English
| MEDLINE | ID: covidwho-897564
ABSTRACT
BACKGROUND:
Humans and viruses have co-evolved for millennia resulting in a complex host genetic architecture. Understanding the genetic mechanisms of immune response to viral infection provides insight into disease etiology and therapeutic opportunities.METHODS:
We conducted a comprehensive study including genome-wide and transcriptome-wide association analyses to identify genetic loci associated with immunoglobulin G antibody response to 28 antigens for 16 viruses using serological data from 7924 European ancestry participants in the UK Biobank cohort.RESULTS:
Signals in human leukocyte antigen (HLA) class II region dominated the landscape of viral antibody response, with 40 independent loci and 14 independent classical alleles, 7 of which exhibited pleiotropic effects across viral families. We identified specific amino acid (AA) residues that are associated with seroreactivity, the strongest associations presented in a range of AA positions within DRß1 at positions 11, 13, 71, and 74 for Epstein-Barr virus (EBV), Varicella zoster virus (VZV), human herpesvirus 7, (HHV7), and Merkel cell polyomavirus (MCV). Genome-wide association analyses discovered 7 novel genetic loci outside the HLA associated with viral antibody response (P < 5.0 × 10-8), including FUT2 (19q13.33) for human polyomavirus BK (BKV), STING1 (5q31.2) for MCV, and CXCR5 (11q23.3) and TBKBP1 (17q21.32) for HHV7. Transcriptome-wide association analyses identified 114 genes associated with response to viral infection, 12 outside of the HLA region, including ECSCR P = 5.0 × 10-15 (MCV), NTN5 P = 1.1 × 10-9 (BKV), and P2RY13 P = 1.1 × 10-8 EBV nuclear antigen. We also demonstrated pleiotropy between viral response genes and complex diseases, from autoimmune disorders to cancer to neurodegenerative and psychiatric conditions.CONCLUSIONS:
Our study confirms the importance of the HLA region in host response to viral infection and elucidates novel genetic determinants beyond the HLA that contribute to host-virus interaction.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Diseases
/
Genetic Predisposition to Disease
/
Disease Susceptibility
/
Host-Pathogen Interactions
Type of study:
Cohort study
/
Etiology study
/
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Genome Med
Year:
2020
Document Type:
Article
Affiliation country:
S13073-020-00790-x
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