Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants
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 a...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61330-y |
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| author | Franz Förster David Emmert Katrin Horn Janne Pott Johannes Frasnelli Mohammed Aslam Imtiaz Konstantinos Melas Valentina Talevi Honglei Chen Christoph Engel Michele Filosi Myriam Fornage Martin Gögele Markus Löffler Thomas H. Mosley Cristian Pattaro Peter Pramstaller Srishti Shrestha N. Ahmad Aziz Monique M. B. Breteler Kerstin Wirkner Markus Scholz Christian Fuchsberger |
| author_facet | Franz Förster David Emmert Katrin Horn Janne Pott Johannes Frasnelli Mohammed Aslam Imtiaz Konstantinos Melas Valentina Talevi Honglei Chen Christoph Engel Michele Filosi Myriam Fornage Martin Gögele Markus Löffler Thomas H. Mosley Cristian Pattaro Peter Pramstaller Srishti Shrestha N. Ahmad Aziz Monique M. B. Breteler Kerstin Wirkner Markus Scholz Christian Fuchsberger |
| author_sort | Franz Förster |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-da9076cd31d0401a9ea696d5ab12ddf5 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-da9076cd31d0401a9ea696d5ab12ddf52025-08-20T03:42:55ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-61330-yGenome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variantsFranz Förster0David Emmert1Katrin Horn2Janne Pott3Johannes Frasnelli4Mohammed Aslam Imtiaz5Konstantinos Melas6Valentina Talevi7Honglei Chen8Christoph Engel9Michele Filosi10Myriam Fornage11Martin Gögele12Markus Löffler13Thomas H. Mosley14Cristian Pattaro15Peter Pramstaller16Srishti Shrestha17N. Ahmad Aziz18Monique M. B. Breteler19Kerstin Wirkner20Markus Scholz21Christian Fuchsberger22Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Medical Faculty, Leipzig UniversityInstitute for Biomedicine, Eurac ResearchInstitute for Medical Informatics, Statistics and Epidemiology (IMISE), Medical Faculty, Leipzig UniversityInstitute for Medical Informatics, Statistics and Epidemiology (IMISE), Medical Faculty, Leipzig UniversityInstitute for Biomedicine, Eurac ResearchGerman Centre for Neurodegenerative Diseases (DZNE), Population Health SciencesGerman Centre for Neurodegenerative Diseases (DZNE), Population Health SciencesGerman Centre for Neurodegenerative Diseases (DZNE), Population Health SciencesDepartment of Epidemiology and Biostatistics, Michigan State UniversityInstitute for Medical Informatics, Statistics and Epidemiology (IMISE), Medical Faculty, Leipzig UniversityInstitute for Biomedicine, Eurac ResearchBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science at HoustonInstitute for Biomedicine, Eurac ResearchInstitute for Medical Informatics, Statistics and Epidemiology (IMISE), Medical Faculty, Leipzig UniversityThe Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical CenterInstitute for Biomedicine, Eurac ResearchInstitute for Biomedicine, Eurac ResearchThe Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical CenterGerman Centre for Neurodegenerative Diseases (DZNE), Population Health SciencesGerman Centre for Neurodegenerative Diseases (DZNE), Population Health SciencesLIFE - Leipzig Research Centre for Civilization Diseases, Medical Faculty, Leipzig UniversityInstitute for Medical Informatics, Statistics and Epidemiology (IMISE), Medical Faculty, Leipzig UniversityInstitute for Biomedicine, Eurac ResearchAbstract 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.https://doi.org/10.1038/s41467-025-61330-y |
| spellingShingle | Franz Förster David Emmert Katrin Horn Janne Pott Johannes Frasnelli Mohammed Aslam Imtiaz Konstantinos Melas Valentina Talevi Honglei Chen Christoph Engel Michele Filosi Myriam Fornage Martin Gögele Markus Löffler Thomas H. Mosley Cristian Pattaro Peter Pramstaller Srishti Shrestha N. Ahmad Aziz Monique M. B. Breteler Kerstin Wirkner Markus Scholz Christian Fuchsberger Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants Nature Communications |
| title | Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants |
| title_full | Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants |
| title_fullStr | Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants |
| title_full_unstemmed | Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants |
| title_short | Genome-wide association meta-analysis of human olfactory identification discovers sex-specific and sex-differential genetic variants |
| title_sort | genome wide association meta analysis of human olfactory identification discovers sex specific and sex differential genetic variants |
| url | https://doi.org/10.1038/s41467-025-61330-y |
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