Unbiased metabolome screen links serum urate to risk of Alzheimer's disease

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dc.authoridMotsi, Gamuchirai Kimberly/0000-0002-4296-7290
dc.authoridCooper-Knock, Johnathan/0000-0002-0873-8689
dc.contributor.authorSanli, Beyazit Abdurrahman
dc.contributor.authorWhittaker, Katherine J.
dc.contributor.authorMotsi, Gamuchirai K.
dc.contributor.authorShen, Emery
dc.contributor.authorJulian, Thomas H.
dc.contributor.authorCooper-Knock, Johnathan
dc.date.accessioned2024-11-07T13:34:27Z
dc.date.available2024-11-07T13:34:27Z
dc.date.issued2022
dc.departmentNiğde Ömer Halisdemir Üniversitesi
dc.description.abstractAlzheimer's disease (AD) is a progressive and fatal neurodegenerative disease caused by a combination of genetic and environmental risk factors. The serum metabolome refers to a set of small-molecules which are an important determinant of cellular health. We obtained genome-wide association study (GWAS) summary statistics for serum concentrations of 376 metabolites which were population matched with 2 GWAS studies of AD. For each metabolite we performed 2-sample MR (2SMR) using an inverse variance weighted (IVW) estimate for significance testing. After Bonferroni multiple testing correction one metabo-lite was causally linked to AD in both GWAS: serum urate. This result was supported by robust 2SMR measures and sensitivity analyses. We applied 2SMR to test for a causal relationship between serum urate and other neurodegenerative diseases: Parkinson disease (PD) and Amyotrophic lateral sclerosis (ALS). In ALS but not PD we identified a nominally significant link between serum urate and disease-risk, although in this case increased serum urate was protective. We conclude that serum urate is a modulator of risk for neurodegeneration. Our work has implications for the design of preventative interventions.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license( http://creativecommons.org/licenses/by/4.0/ )
dc.description.sponsorshipWellcome Trust fellowship [216596/Z/19/Z]; Wellcome Trust [216596/Z/19/Z] Funding Source: Wellcome Trust
dc.description.sponsorshipThis work was supported by a Wellcome Trust fellowship [216596/Z/19/Z to J.C.-K] .
dc.identifier.doi10.1016/j.neurobiolaging.2022.09.004
dc.identifier.endpage176
dc.identifier.issn0197-4580
dc.identifier.issn1558-1497
dc.identifier.pmid36206691
dc.identifier.scopus2-s2.0-85139364580
dc.identifier.scopusqualityQ1
dc.identifier.startpage167
dc.identifier.urihttps://doi.org/10.1016/j.neurobiolaging.2022.09.004
dc.identifier.urihttps://hdl.handle.net/11480/15980
dc.identifier.volume120
dc.identifier.wosWOS:000873957000001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Science Inc
dc.relation.ispartofNeurobiology of Aging
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241106
dc.subjectAlzheimer?s Disease
dc.subjectSerum urate
dc.subjectMetabolome
dc.subjectMendelian Randomization
dc.titleUnbiased metabolome screen links serum urate to risk of Alzheimer's disease
dc.typeArticle

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