To date, little is known about the role of olfactory receptor (OR) genes on smell performance. Thanks to the availability of whole-genome sequencing data of 802 samples, we identified 41 knockout (KO) OR genes (i.e., carriers of Loss of Function variants) and evaluated their effect on odor discrimination in 218 Italian individuals through recursive partitioning analysis. Furthermore, we checked the expression of these genes in human and mouse tissues using publicly available data and the presence of organ-related diseases in human KO (HKO) individuals for OR expressed in non-olfactory tissues (Fisher test). The recursive partitioning analysis showed that age and the high number (burden) of OR-KO genes impact the worsening of odor discrimination (p-value < 0.05). Human expression data showed that 33/41 OR genes are expressed in the olfactory system (OS) and 27 in other tissues. Sixty putative mouse homologs of the 41 humans ORs have been identified, 58 of which are expressed in the OS and 37 in other tissues. No association between OR-KO individuals and pathologies has been detected. In conclusion, our work highlights the role of the burden of OR-KO genes in worse odor discrimination.
Keywords: gene expression; human knockouts; loss of function variants; odor discrimination; olfactory receptors genes; whole-genome sequencing.