89: Genetics of Smell and Sex Differences

Förster F et al., Nature Communications - This GWAMA of up to 21,495 European-ancestry participants used the Sniffin' Sticks odour identification test to map genetic variants influencing identification of twelve odours and an identification score. The study reports ten independent loci (seven novel), sex-stratified effects, and a Mendelian randomization finding that Alzheimer's genetic risk negatively affects smell identification. Key terms: olfaction, GWAS, sex-specific genetics, olfactory receptors, Mendelian randomization.

Study Highlights:
A meta-analysis across four cohorts (n≤21,495) tested identification of twelve Sniffin' Sticks odours and a total identification score. Ten independent loci reached genome-wide significance, seven of them novel, with most loci located in olfactory receptor clusters and other plausible candidates (e.g., ADCY2). Sex-stratified analyses identified female-specific loci and one sex-differential locus, with candidate genes showing predicted androgen response elements. Two-sample Mendelian randomization detected a negative causal effect of Alzheimer's disease genetic risk on the identification score while sex hormones showed no robust causal effect.

Conclusion:
The study adds seven novel loci for odour identification, reveals sex-specific genetic effects at multiple loci, and provides evidence that genetic risk for Alzheimer's disease contributes to poorer global olfactory identification; further molecular and larger cross-ancestry studies are needed to extend these findings.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants

First author:
Förster F

Journal:
Nature Communications

DOI:
10.1038/s41467-025-61330-y

Reference:
Förster F., Emmert D., Horn K., et al. Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants. Nature Communications (2025). DOI: https://doi.org/10.1038/s41467-025-61330-y

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/base-by-base-ep89-olfactory-gwas-sex-differences

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-07-28.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript's coverage of the article's methods and results: GWAMA findings (ten loci, seven novel, two female-specific, one sex-differential), candidate genes (ADCY2, OR clusters, TAAR5, FBXL17, OR11H7), the pineapple odor driving the overall score, sex-differentiation mechanisms (AREs), Mendelian randomiza
- transcript topics: Sniffin' Sticks test and scoring; Genome-wide association meta-analysis (GWAMA) and loci; Loci near olfactory receptor (OR) clusters and candidate genes; Pineapple odor driving the global identification score; Sex-specific and sex-differential SNP effects and androgen/estrogen regulatory elements; Mendelian randomization: hormones and neurodegenerative diseases

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed...