ABSTRACT
Using online surveys, we collected data regarding COVID-19-related loss of smell or taste from 69,841 individuals. We performed a multi-ancestry genome-wide association study and identified a genome-wide significant locus in the vicinity of the UGT2A1 and UGT2A2 genes. Both genes are expressed in the olfactory epithelium and play a role in metabolizing odorants. These findings provide a genetic link to the biological mechanisms underlying COVID-19-related loss of smell or taste.
Subject(s)
Ageusia/genetics , Anosmia/genetics , COVID-19/genetics , Genetic Loci , Genome-Wide Association Study , Glucuronosyltransferase/genetics , UDP-Glucuronosyltransferase 1A9/genetics , Adult , Aged , Ageusia/enzymology , Anosmia/enzymology , Female , Humans , Male , Middle Aged , Phenotype , Polymorphism, Single Nucleotide/genetics , Sample SizeABSTRACT
Severe acute respiratory syndrome (SARS) coronavirus2 (SARSCoV2) enters into human host cells via mechanisms facilitated mostly by angiotensinconverting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). New loss of smell (anosmia/hyposmia) is now recognized as a COVID19 related symptom, which may be caused by SARSCoV2 infection and damage of the olfactory receptor (OR) cells in the nasal neuroepithelium and/or central involvement of the olfactory bulb. ORs are also expressed peripherally (e.g., in tissues of the gastrointestinal and respiratory systems) and it is possible that their local functions could also be impaired by SARSCoV2 infection of these tissues. Using Gene Expression Profiling Interactive Analysis, The Cancer Genome Atlas, GenotypeTissue Expression, cBioPortal and Shiny Methylation Analysis Resource Tool, we highlight the expression of peripheral ORs in both healthy and malignant tissues, and describe their coexpression with key mediators of SARSCoV2 infection, such as ACE2 and TMPRSS2, as well as cathepsin L (CTSL; another cellular protease mediating SARSCoV2 infection of host cells). A wide expression profile of peripheral ORs was noted, particularly in tissues such as the prostate, testis, thyroid, brain, liver, kidney and bladder, as well as tissues with known involvement in cardiometabolic disease (e.g., the adipose tissue, pancreas and heart). Among these, OR51E2, in particular, was significantly upregulated in prostate adenocarcinoma (PRAD) and coexpressed primarily with TMPRSS2. Functional networks of this OR were further analysed using the GeneMANIA interactive tool, showing that OR51E2 interacts with a plethora of genes related to the prostate. Further in vitro and clinical studies are clearly required to elucidate the role of ORs, both at the olfactory level and the periphery, in the context of COVID19.