TY  - JOUR
AU  - Förster, Franz
AU  - Emmert, David
AU  - Horn, Katrin
AU  - Pott, Janne
AU  - Frasnelli, Johannes
AU  - Imtiaz, Mohammed Aslam
AU  - Melas, Konstantinos
AU  - Talevi, Valentina
AU  - Chen, Honglei
AU  - Engel, Christoph
AU  - Filosi, Michele
AU  - Fornage, Myriam
AU  - Gögele, Martin
AU  - Löffler, Markus
AU  - Mosley, Thomas H
AU  - Pattaro, Cristian
AU  - Pramstaller, Peter
AU  - Shrestha, Srishti
AU  - Aziz, N Ahmad
AU  - Breteler, Monique M B
AU  - Wirkner, Kerstin
AU  - Scholz, Markus
AU  - Fuchsberger, Christian
TI  - Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-00770
SP  - 5434
PY  - 2025
AB  - Smelling is a human sense, expressing strong sexual dimorphisms. We aim to improve the knowledge of the genetics of human olfactory perception by performing an exploratory genome-wide association meta-analysis of up to 21,495 individuals of European ancestry. By sex-stratified and overall analysis of the identification of twelve odours and an identification score, we discovered ten independent loci, seven of them novel, with trait-wise genome-wide significance (p < 5 × 10-8) involving five odours. Seven of these loci, including four novel ones, are also significant using a stricter study-wide significance threshold (p < 3.85 × 10-9). Loci were predominantly located within clusters of olfactory receptors. Two loci were female-specific while one was sex-differential with respective candidate genes containing androgen response elements. Two-sample Mendelian randomization was applied to search for causal relationships between sex hormones, odour identification and neurodegenerative diseases. A causal negative effect was detected for Alzheimer's disease on the identification score. These findings deepen our understanding of the genetic basis of olfactory perception and its interaction with sex, prioritizing mechanisms for further molecular research.
KW  - Female
KW  - Humans
KW  - Male
KW  - Alzheimer Disease: genetics
KW  - Genetic Variation
KW  - Genome-Wide Association Study
KW  - Mendelian Randomization Analysis
KW  - Odorants: analysis
KW  - Olfactory Perception: genetics
KW  - Polymorphism, Single Nucleotide
KW  - Receptors, Odorant: genetics
KW  - Sex Characteristics
KW  - Smell: genetics
KW  - White People: genetics
KW  - Receptors, Odorant (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40593737
C2  - pmc:PMC12219263
DO  - DOI:10.1038/s41467-025-61330-y
UR  - https://pub.dzne.de/record/279439
ER  -