TY  - JOUR
AU  - Imtiaz, Mohammed Aslam
AU  - Melas, Konstantinos
AU  - Tin, Adrienne
AU  - Talevi, Valentina
AU  - Chen, Honglei
AU  - Fornage, Myriam
AU  - Shrestha, Srishti
AU  - Gögele, Martin
AU  - Emmert, David
AU  - Pattaro, Cristian
AU  - Pramstaller, Peter
AU  - Förster, Franz
AU  - Horn, Katrin
AU  - Mosley, Thomas H
AU  - Fuchsberger, Christian
AU  - Scholz, Markus
AU  - Breteler, Monique M B
AU  - Aziz, N. Ahmad
TI  - Genome-wide association study meta-analysis uncovers novel genetic variants associated with olfactory dysfunction.
JO  - BMC genomic data
VL  - 26
IS  - 1
SN  - 2730-6844
CY  - [London]
PB  - BioMed Central
M1  - DZNE-2025-01091
SP  - 64
PY  - 2025
AB  - Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown. Therefore, here we aimed to elucidate its genetic architecture through a genome-wide association study meta-analysis (GWMA).This GWMA included the participants of European ancestry (N = 22,730) enrolled in four different large population-based studies followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). Olfactory dysfunction was assessed using a 12-item smell identification test.GWMA revealed a novel genome-wide significant locus (tagged by single nucleotide polymorphism rs11228623 at the 11q12 locus) associated with olfactory dysfunction. Gene-based analysis revealed a high enrichment for olfactory receptor genes in this region. Phenome-wide association studies demonstrated associations between genetic variants related to olfactory dysfunction and blood cell counts, kidney function, skeletal muscle mass, cholesterol levels and cardiovascular disease. Using individual-level data, we also confirmed and quantified the strength of these associations on a phenotypic level. Moreover, employing two-sample Mendelian Randomization analyses, we found evidence for causal associations between olfactory dysfunction and these phenotypes.Our findings provide novel insights into the genetic architecture of the sense of smell and highlight its importance for many aspects of human health. Moreover, these findings could facilitate the identification and monitoring of individuals at increased risk of olfactory dysfunction and associated diseases.
KW  - Humans
KW  - Genome-Wide Association Study
KW  - Olfaction Disorders: genetics
KW  - Polymorphism, Single Nucleotide
KW  - Male
KW  - Female
KW  - Genetic Predisposition to Disease
KW  - Receptors, Odorant: genetics
KW  - Middle Aged
KW  - White People: genetics
KW  - Aged
KW  - White
KW  - Anthropometric (Other)
KW  - Biochemical (Other)
KW  - Gene-mapping (Other)
KW  - Genome-wide association meta-analysis (Other)
KW  - Odor identification test (Other)
KW  - Olfactory dysfunction (Other)
KW  - PheWAS (Other)
KW  - Sense of smell (Other)
KW  - Two-sample MR (Other)
KW  - Receptors, Odorant (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40963118
DO  - DOI:10.1186/s12863-025-01360-z
UR  - https://pub.dzne.de/record/281276
ER  -