Key Questions Answered
Q: What did the study reveal about the genetics of smell?
A: A large genetic analysis identified ten genomic regions associated with the ability to recognize particular odors, seven of which are newly reported discoveries.
Q: How do sex differences influence smell perception?
A: Three of the identified regions show effects that differ between men and women, offering genetic explanations for changes in smell sensitivity related to menstrual cycles, pregnancy, or other sex-specific hormonal states.
Q: What is the link between smell and Alzheimer’s disease?
A: The study found evidence of a genetic connection between odor identification ability and Alzheimer’s disease risk, reinforcing the idea that changes in the sense of smell can be an early sign of neurodegeneration.
Summary: In a genome-wide meta-analysis of more than 21,000 people of European ancestry, researchers uncovered ten distinct genetic loci associated with the perception of specific odors; seven of those loci had not been reported before. Several loci act differently by sex, and one analysis suggested a causal relationship between Alzheimer’s disease risk and reduced odor identification. These results highlight the genetic complexity of olfaction and point to sex-specific biological mechanisms that may be important for diagnosis and early detection of neurodegenerative disease.
Key Facts
- New Genetic Associations: Ten genomic regions were linked to odor identification; seven are novel discoveries.
- Sex-Specific Effects: Three loci displayed different effects in men and women, likely influenced by sex hormones.
- Alzheimer’s Connection: Genetic analyses indicate a relationship between odor detection ability and Alzheimer’s disease risk, suggesting olfaction may serve as an early marker of neurodegeneration.
Source: University of Leipzig
Overview
Olfaction is one of the least-studied human senses, yet disorders of smell can substantially reduce quality of life and may reveal underlying medical conditions. This study explores the genetic foundations of human odor identification using genome-wide association methods applied to a large cohort of European-descent participants, with particular attention to differences between sexes.
Genetic architecture and sex differences in smell
Researchers performed a meta-analysis combining data from multiple studies, totalling up to 21,495 participants. They examined identification performance for twelve everyday odors and also computed an overall identification score. The analysis discovered ten independent loci reaching genome-wide significance, five of which were associated with specific odors. Seven loci remained significant under a more stringent study-wide threshold. Many of these loci lie within clusters of olfactory receptor genes, underlining the role of receptor variation in perceiving distinct smells.
Importantly, two loci were significant only in female-stratified analyses, and one locus showed a sex-differential effect. Candidate genes near these regions include regulatory elements related to androgen response, indicating that sex hormones may modulate olfactory perception at the genetic level. These findings help explain common observations that smell sensitivity changes with menstrual cycles, pregnancy, or other hormone-driven states, and they support the development of sex-aware diagnostic approaches.
Olfaction and neurodegenerative disease
The team also used two-sample Mendelian randomization to explore causal relationships between sex hormones, odor identification, and neurodegenerative conditions. This approach provided evidence for a negative causal effect of Alzheimer’s disease risk on overall odor identification ability, reinforcing the idea that early decline in smell can be an indicator of neurodegeneration. While the genetic links do not prove that olfactory loss causes Alzheimer’s, they support the use of olfactory testing as a potentially valuable screening tool in at-risk populations.
How the study measured smell
Participants in the Leipzig LIFE Adult Study and partner cohorts were asked to identify twelve common everyday odors delivered in standardized scent pens. Responses were matched to participants’ genetic data and combined across cohorts in a large-scale meta-analysis led by the Institute for Medical Informatics, Statistics and Epidemiology at Leipzig University.
A larger national study—the German National Cohort (NAKO Gesundheitsstudie), in which Leipzig University participates—is currently collecting odor identification data from roughly 200,000 people. Researchers expect those data to enable finer-grained analyses of genetic and sex-specific influences on olfaction.
About this genetics and olfaction research news
Author: Anne Grimm
Source: University of Leipzig
Contact: Anne Grimm – University of Leipzig
Image: Image credited to Neuroscience News
Original Research: Open access.
Title: “Genome-wide association meta analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants” by Markus Scholz et al. Published in Nature Communications. DOI: 10.1038/s41467-025-61330-y
Abstract
Genome-wide association meta analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants
Smell is a human sense with pronounced sexual dimorphism. To advance understanding of the genetics behind olfactory perception, the authors conducted an exploratory genome-wide association meta-analysis including up to 21,495 individuals of European ancestry. Through sex-stratified and combined analyses of identification performance for twelve odors and a composite identification score, they identified ten independent loci—seven of them novel—with trait-wise genome-wide significance (p < 5 × 10−8) across five odors. Seven loci, including four novel ones, reached a stricter study-wide significance threshold (p < 3.85 × 10−9). Many loci mapped to clusters of olfactory receptor genes. Two loci were female-specific and one showed sex-differential effects, with candidate genes containing androgen response elements. Mendelian randomization analyses probed causal links among sex hormones, odor identification, and neurodegenerative diseases, revealing a causal negative effect of Alzheimer’s disease on the odor identification score. These findings enrich our knowledge of the genetic basis of olfactory perception, emphasize the interaction with sex, and highlight molecular mechanisms for further study.