193 - Association between olfactory function and cognition in a high cardiovascular risk population: Construction of a polygenic risk score including olfactory receptor genes for Mendelian randomization. (ID 949)
Abstract
Background and Aims
Olfactory impairment has been associated with increased mortality, mainly cardiovascular mortality and neurodegenerative diseases. Therefore, there is great interest in the measurement of olfactory capacity, to analyze its association with cardiovascular and cognitive phenotypes in several populations. However, measuring smell perception is a time-consuming task and the vast majority of existing cohorts are lacking this measure. Smell perception is genetically determined and some strong associations of specific odorant with single nucleotide polymorphisms (SNPs) in olfactory receptor genes (OR) have been reported. Therefore, our aim was to create a genomic biomarker consisting of a polygenic genetic risk score (GRS) including SNPs in OR as candidate genes.
Methods
We analyzed the olfactory function in 300 participants in the PREDIMED Plus-Valencia study using the validated Sniffin´Sticks Extended test. We calculated the “TDI score” and performed a genome-wide genotyping for the association between the OR polymorphisms and the TDI score and created a GRS with the most relevant SNPs. We also measured cognitive performance by validated tests.
Results
The most relevant ORs included in the GRS were: OR51E1, OR51B2, OR1J2, OR51G1, OR4D5 and OR5AR1, among others. This GRS (unweighted and weighted) was strongly and directly associated with the olfactory function (r=0.42; P=4x10-13 and r=0.47; P=2x10-16, for the unweighted and weighted, respectively). Moreover, in the Mendelian randomization analysis, the GRS was significantly and directly associated with verbal fluency, even after multivariate adjustment, suggesting causality.
Conclusions
We developed a genetic biomarker for olfactory function in this population. Validation in other populations is required.
