Investigating Olfactory Gene Variation and Odour Identification in Older Adults.

Siddharth Raj,Karen A Mather,David Ames,Margaret J Wright,Julian N Trollor,John B Kwok,Perminder S Sachdev,Nicola J Armstrong,Peter R Schofield,Anbupalam Thalamuthu,Henry Brodaty

doi:10.3390/genes12050669

Abstract

Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. The olfactory receptor (OR) gene family is the largest in the human genome and responsible for overall odour identification. In this study, we sought to find olfactory gene family variants associated with individual and overall odour identification and to examine the relationships between polygenic risk scores (PRS) for olfactory-related phenotypes and olfaction. Participants were Caucasian older adults from the Sydney Memory and Ageing Study and the Older Australian Twins Study with genome-wide genotyping data (n = 1395, mean age = 75.52 ± 6.45). The Brief-Smell Identification Test (BSIT) was administered in both cohorts. PRS were calculated from independent GWAS summary statistics for Alzheimer’s disease (AD), white matter hyperintensities (WMH), Parkinson’s disease (PD), hippocampal volume and smoking. Associations with olfactory receptor genes (n = 967), previously identified candidate olfaction-related SNPs (n = 36) and different PRS with BSIT scores (total and individual smells) were examined. All of the relationships were analysed using generalised linear mixed models (GLMM), adjusted for age and sex. Genes with suggestive evidence for odour identification were found for 8 of the 12 BSIT items. Thirteen out of 36 candidate SNPs previously identified from the literature were suggestively associated with several individual BSIT items but not total score. PRS for smoking, WMH and PD were negatively associated with chocolate identification. This is the first study to conduct genetic analyses with individual odorant identification, which found suggestive olfactory-related genes and genetic variants for multiple individual BSIT odours. Replication in independent and larger cohorts is needed.

Highlights

Olfaction is a trait that is important for nutrition, well-being and quality of life
We aim to identify genes and Single Nucleotide Polymorphisms (SNPs) associated with age-related olfactory identification in community-dwelling older adults
We examine the associations of polygenic risk scores (PRS) for tobacco smoking, Alzheimer’s disease (AD), Parkinson’s disease (PD), white matter hyperintensities (WMH), and hippocampal volume (HV) with olfactory identification to ascertain whether genetic risk for these phenotypes is associated with olfaction

Summary

Introduction

Olfaction is a trait that is important for nutrition, well-being and quality of life. Ageing is associated with a decline in the ability to smell with more than 75% of individuals over 80 years old exhibiting a major olfactory deficit [2]. Impaired olfactory ability has been linked to hippocampal atrophy, high white matter hyperintensity (WMH) volumes and increased amyloid burden [1,3]. It has been associated with the incidence of neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), global cognitive performance in older adults [1,3,4] and increased risk of mortality [5]. Long term exposure to chemicals, for example via smoking, can induce ciliopathies that may contribute to the observed decline in smell with ageing [8]

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