Host genetic loci LZTFL1 and CCL2 associated with SARS-CoV-2 infection and severity of COVID-19.
Int J Infect Dis
; 122: 427-436, 2022 Sep.
Article
in English
| MEDLINE | ID: covidwho-1907179
ABSTRACT
OBJECTIVES:
Host genetic factors contribute to the variable severity of COVID-19. We examined genetic variants from genome-wide association studies and candidate gene association studies in a cohort of patients with COVID-19 and investigated the role of early SARS-CoV-2 strains in COVID-19 severity.METHODS:
This case-control study included 123 COVID-19 cases (hospitalized or ambulatory) and healthy controls from the state of Baden-Wuerttemberg, Germany. We genotyped 30 single nucleotide polymorphisms, using a custom-designed panel. Cases were also compared with the 1000 genomes project. Polygenic risk scores were constructed. SARS-CoV-2 genomes from 26 patients with COVID-19 were sequenced and compared between ambulatory and hospitalized cases, and phylogeny was reconstructed.RESULTS:
Eight variants reached nominal significance and two were significantly associated with at least one of the phenotypes "susceptibility to infection", "hospitalization", or "severity" rs73064425 in LZTFL1 (hospitalization and severity, P <0.001) and rs1024611 near CCL2 (susceptibility, including 1000 genomes project, P = 0.001). The polygenic risk score could predict hospitalization. Most (23/26, 89%) of the SARS-CoV-2 genomes were classified as B.1 lineage. No associations of SARS-CoV-2 mutations or lineages with severity were observed.CONCLUSION:
These host genetic markers provide insights into pathogenesis and enable risk classification. Variants which reached nominal significance should be included in larger studies.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Transcription Factors
/
Chemokine CCL2
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Int J Infect Dis
Journal subject:
Communicable Diseases
Year:
2022
Document Type:
Article
Affiliation country:
J.ijid.2022.06.030
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