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@ARTICLE{Imtiaz:271700,
author = {Imtiaz, Mohammed Aslam and Melas, Konstantinos and Tin,
Adrienne and Talevi, Valentina and Chen, Honglei and
Fornage, Myriam and Shrestha, Srishti and Gögele, Martin
and Emmert, David and Pattaro, Cristian and Pramstaller,
Peter and Förster, Franz and Horn, Katrin and Mosley,
Thomas H and Fuchsberger, Christian and Scholz, Markus and
Breteler, Monique and Aziz, N. Ahmad},
title = {{G}enome-{W}ide {A}ssociation {S}tudy {M}eta-{A}nalysis
{U}ncovers {N}ovel {G}enetic {V}ariants {A}ssociated with
{O}lfactory {D}ysfunction.},
reportid = {DZNE-2024-01055},
year = {2024},
abstract = {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.To
identify the genetic loci associated with olfactory
dysfunction in the general population.This genome-wide
association study meta-analysis (GWMA) included 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).
The data analysis was performed from March 2023 through June
2024.Genome-wide single nucleotide polymorphisms.Olfactory
dysfunction was the outcome and assessed using a 12-item
smell identification test.GWMA revealed a novel genome-wide
significant locus (tagged by rs11228623 at 11q12) 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.These findings
provide novel insights into the genetic architecture of the
sense of smell and highlight its importance for many aspects
of human health.What is the genetic basis of olfactory
dysfunction, and is it causally related to adverse health
outcomes?This genome-wide association study meta-analysis
(GWMA) of 22,730 European and 1,030 African participants
identified a novel genomic locus, enriched for olfactory
receptor genes, robustly associated with olfactory
dysfunction. Two-sample Mendelian Randomization analyses
provided evidence for causal associations of olfactory
dysfunction with biochemical, anthropometric and
cardiovascular health outcomes.These findings provide new
insights into the genetic architecture of olfaction and
implicate olfactory dysfunction as a causal risk factor for
many aspects of human health.},
cin = {AG Aziz / AG Breteler},
cid = {I:(DE-2719)5000071 / I:(DE-2719)1012001},
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)25},
pubmed = {pmid:39148842},
pmc = {pmc:PMC11326328},
doi = {10.1101/2024.08.09.24311665},
url = {https://pub.dzne.de/record/271700},
}