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000271700 0247_ $$2pmid$$apmid:39148842
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000271700 0247_ $$2doi$$a10.1101/2024.08.09.24311665
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000271700 037__ $$aDZNE-2024-01055
000271700 041__ $$aEnglish
000271700 1001_ $$0P:(DE-2719)9002347$$aImtiaz, Mohammed Aslam$$b0$$eFirst author
000271700 245__ $$aGenome-Wide Association Study Meta-Analysis Uncovers Novel Genetic Variants Associated with Olfactory Dysfunction.
000271700 260__ $$c2024
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000271700 520__ $$aOlfactory 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.
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000271700 7001_ $$0P:(DE-2719)9001389$$aMelas, Konstantinos$$b1
000271700 7001_ $$0P:(DE-HGF)0$$aTin, Adrienne$$b2
000271700 7001_ $$0P:(DE-2719)9001002$$aTalevi, Valentina$$b3
000271700 7001_ $$0P:(DE-HGF)0$$aChen, Honglei$$b4
000271700 7001_ $$0P:(DE-HGF)0$$aFornage, Myriam$$b5
000271700 7001_ $$0P:(DE-HGF)0$$aShrestha, Srishti$$b6
000271700 7001_ $$0P:(DE-HGF)0$$aGögele, Martin$$b7
000271700 7001_ $$0P:(DE-HGF)0$$aEmmert, David$$b8
000271700 7001_ $$0P:(DE-HGF)0$$aPattaro, Cristian$$b9
000271700 7001_ $$0P:(DE-HGF)0$$aPramstaller, Peter$$b10
000271700 7001_ $$0P:(DE-HGF)0$$aFörster, Franz$$b11
000271700 7001_ $$0P:(DE-HGF)0$$aHorn, Katrin$$b12
000271700 7001_ $$0P:(DE-HGF)0$$aMosley, Thomas H$$b13
000271700 7001_ $$0P:(DE-HGF)0$$aFuchsberger, Christian$$b14
000271700 7001_ $$0P:(DE-HGF)0$$aScholz, Markus$$b15
000271700 7001_ $$0P:(DE-2719)2810403$$aBreteler, Monique$$b16
000271700 7001_ $$0P:(DE-2719)2812578$$aAziz, N. Ahmad$$b17$$eLast author
000271700 773__ $$a10.1101/2024.08.09.24311665
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000271700 9201_ $$0I:(DE-2719)5000071$$kAG Aziz$$lPopulation & Clinical Neuroepidemiology$$x0
000271700 9201_ $$0I:(DE-2719)1012001$$kAG Breteler$$lPopulation Health Sciences$$x1
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