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@ARTICLE{Frster:279439,
author = {Förster, Franz and Emmert, David and Horn, Katrin and
Pott, Janne and Frasnelli, Johannes and Imtiaz, Mohammed
Aslam and Melas, Konstantinos and Talevi, Valentina and
Chen, Honglei and Engel, Christoph and Filosi, Michele and
Fornage, Myriam and Gögele, Martin and Löffler, Markus and
Mosley, Thomas H and Pattaro, Cristian and Pramstaller,
Peter and Shrestha, Srishti and Aziz, N Ahmad and Breteler,
Monique M B and Wirkner, Kerstin and Scholz, Markus and
Fuchsberger, Christian},
title = {{G}enome-wide association meta-analysis of human olfactory
identification discovers sex-specific and sex-differential
genetic variants.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DZNE-2025-00770},
pages = {5434},
year = {2025},
abstract = {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.},
keywords = {Female / Humans / Male / Alzheimer Disease: genetics /
Genetic Variation / Genome-Wide Association Study /
Mendelian Randomization Analysis / Odorants: analysis /
Olfactory Perception: genetics / Polymorphism, Single
Nucleotide / Receptors, Odorant: genetics / Sex
Characteristics / Smell: genetics / White People: genetics /
Receptors, Odorant (NLM Chemicals)},
cin = {AG Breteler / AG Aziz},
ddc = {500},
cid = {I:(DE-2719)1012001 / I:(DE-2719)5000071},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
experiment = {EXP:(DE-2719)Rhineland Study-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40593737},
pmc = {pmc:PMC12219263},
doi = {10.1038/s41467-025-61330-y},
url = {https://pub.dzne.de/record/279439},
}