Genetic Variations in Bitter Taste Receptors and COVID-19 in the Canadian Longitudinal Study on Aging

<b>Background/Objectives</b>: Bitter Taste Receptors (encoded by <i>TAS2R</i> genes) are expressed in mucosal and bronchial epithelia, as well as in immune cells, contributing to defense against airborne pathogens such as SARS-CoV-2. Data on single-nucleotide polymorphisms (SNPs) in <i>TAS2R</i> genes or pseudogenes in COVID-19 are limited. This study examined the association between <i>TAS2R</i> SNPs and COVID-19 infection and seroconversion in European individuals participating in the Canadian Longitudinal Study on Aging. <b>Methods</b>: Data from the Genome-wide Genetic Data, Comprehensive Baseline (version 7.0), Follow-up 2 (version 1.1), COVID-19 Questionnaire Study (4-2020 to 12-2020), and COVID-19 Seroprevalence (Antibody) Study (11-2020 to 7-2021) datasets were accessed. Associations of <i>TAS2R</i> SNPS with COVID-19 infection or seroconversion were determined using logistic regression adjusted for sociodemographics, genetic principal components, smoking, vaccine doses, and chronic medical conditions (diabetes, immune-mediated inflammatory diseases (IMIDs), respiratory disease, and cardiovascular disease). <b>Results</b>: In the COVID-19 Questionnaire Study (N = 14,073), the rs117458236 (C) variant in <i>TAS2R20</i> showed a trend toward an association with COVID-19 infection (OR = 1.95; 95% Confidence Interval (CI): 0.98, 3.51). In the COVID-19 Antibody Study (N = 8313), the rs2234235(G) variant in <i>TAS2R1</i> was associated with anti-nucleocapsid (OR = 1.55; CI: 1.06, 2.20) and anti-spike response (OR = 0.74; CI: 0.57, 0.98); the rs2234010(A) variant in <i>TAS2R5</i> was associated with anti-nucleocapsid (OR = 1.56; CI: 1.08, 2.19); and the rs34039200(A) variant in <i>TAS2R62P</i> was associated with anti-spike (OR = 0.86; CI: 0.77, 0.97). In a subgroup analysis, the rs2234235(G) variant in <i>TAS2R1</i> was associated with a decreased anti-spike response to infection or vaccination in individuals with IMIDs or respiratory disease and an increased risk of SARS-CoV-2 infection. <b>Conclusions</b>: <i>TAS2R</i> variants are associated with COVID-19 infection and vaccine response. These data may inform personalized management and vaccination strategies.