Faculty, Staff and Student Publications
Language
English
Publication Date
9-17-2025
Journal
BMC Genomic Data
DOI
10.1186/s12863-025-01360-z
PMID
40963118
PMCID
PMC12445039
PubMedCentral® Posted Date
9-17-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown. Therefore, here we aimed to elucidate its genetic architecture through a genome-wide association study meta-analysis (GWMA).
Methods: This GWMA included the participants of European ancestry (N = 22,730) enrolled in four different large population-based studies followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). Olfactory dysfunction was assessed using a 12-item smell identification test.
Results: GWMA revealed a novel genome-wide significant locus (tagged by single nucleotide polymorphism rs11228623 at the 11q12 locus) associated with olfactory dysfunction. Gene-based analysis revealed a high enrichment for olfactory receptor genes in this region. Phenome-wide association studies demonstrated associations between genetic variants related to olfactory dysfunction and blood cell counts, kidney function, skeletal muscle mass, cholesterol levels and cardiovascular disease. Using individual-level data, we also confirmed and quantified the strength of these associations on a phenotypic level. Moreover, employing two-sample Mendelian Randomization analyses, we found evidence for causal associations between olfactory dysfunction and these phenotypes.
Conclusions: Our findings provide novel insights into the genetic architecture of the sense of smell and highlight its importance for many aspects of human health. Moreover, these findings could facilitate the identification and monitoring of individuals at increased risk of olfactory dysfunction and associated diseases.
Keywords
Aged, Female, Humans, Male, Middle Aged, Genetic Predisposition to Disease, Genome-Wide Association Study, Olfaction Disorders, Polymorphism, Single Nucleotide, Receptors, Odorant, White People, Black People, Anthropometric, Biochemical, Gene-mapping, Genome-wide association meta-analysis, Odor identification test, Olfactory dysfunction, PheWAS, Sense of smell, Two-sample MR, Genome-wide association meta-analysis, Olfactory dysfunction, Sense of smell, Odor identification test, Gene-mapping, PheWAS, Biochemical, Anthropometric, Two-sample MR
Published Open-Access
yes
Recommended Citation
Imtiaz, Mohammed Aslam; Melas, Konstantinos; Tin, Adrienne; et al., "Genome-Wide Association Study Meta-Analysis Uncovers Novel Genetic Variants Associated With Olfactory Dysfunction" (2025). Faculty, Staff and Student Publications. 1226.
https://digitalcommons.library.tmc.edu/uthsph_docs/1226