ArticleCOVID2025
Gene-Level Analyses of Novel Olfactory-Related Signal from Severe SARS-CoV-2 GWAS Reveal Association with Disease Mortality.
Article in COVID, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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14 authors.
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Abstract
Importance: The coronavirus disease 2019 (COVID-19) was the third leading cause of mortality in the United States for three years in a row. The genetic contributions to disease severity remain unclear and many previously identified single nucleotide polymorphisms (SNPs) have not been replicated nor linked with functional significance. Objective: To identify SNPs associated with mortality among hospitalized COVID-19 patients supplemented by expression quantitative trait loci (eQTL) evidence to infer plausible functional mechanisms related to COVID-19 severity. Design: A quality-controlled genome-wide association study (GWAS) supported by robust gene-level omnibus kernel association tests (SKAT-O), functional prediction, and eQTL analyses of the top GWAS signal. Setting: Massachusetts General Hospital (MGH). Participants: 370 adult ICU patients with SARS-CoV-2 infection and acute hypoxemic respiratory failure and floor patients with mild hypoxemia managed with supplemental oxygen consecutively admitted to MGH between March and June 2020 (Surge 1), and January and March 2021 (Surge 2) with baseline clinical characteristics and demographics collected. Exposures: Low-pass genotyped SNPs from whole blood and aggregated SNP-sets of potential disease susceptibility loci with ±500 kb flanking regions. Main Outcomes & Measures: Genome-wide individual SNP associations and SNP-set associations with mortality outcomes from 370 severe COVID-19 cases. Results: After LD pruning (<0.8) and false discovery rate adjustment (<0.05), we identified rs7420371 G>A of the receptor transporter protein 5 ( Conclusions & Relevance: We discovered a novel, independent, and potentially functional SNP
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