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Nag, A.* ; Kurushima, Y.* ; Bowyer, R.C.E.* ; Wells, P.M.* ; Weiss, S.* ; Pietzner, M.* ; Kocher, T.* ; Raffler, J. ; Völker, U.* ; Mangino, M.* ; Spector, T.D.* ; Milburn, M.V.* ; Kastenmüller, G. ; Mohney, R.P.* ; Suhre, K.* ; Menni, C.* ; Steves, C.J.*

Genome-wide scan identifies novel genetic loci regulating salivary metabolite levels.

Hum. Mol. Genet. 29, 864-875 (2020)
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Open Access Gold (Paid Option)
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Saliva, as a biofluid, is inexpensive and non-invasive to obtain, and provides a vital tool to investigate oral health and its interaction with systemic health conditions. There is growing interest in salivary biomarkers for systemic diseases, notably cardiovascular disease. Whereas hundreds of genetic loci have been shown to be involved in the regulation of blood metabolites, leading to significant insights into the pathogenesis of complex human diseases, little is known about the impact of host genetics on salivary metabolites. Here we report the first genome-wide association study exploring 476 salivary metabolites in 1419 subjects from the Twins UK cohort (discovery phase), followed by replication in the Study of Health in Pomerania (SHIP-2) cohort. A total of 14 distinct locus-metabolite associations were identified in the discovery phase, most of which were replicated in SHIP-2. While only a limited number of the loci that are known to regulate blood metabolites were also associated with salivary metabolites in our study, we identified several novel saliva-specific locus-metabolite associations, including associations for the AGMAT (with the metabolites 4-guanidinobutanoate and beta-guanidinopropanoate), ATP13A5 (with the metabolite creatinine) and DPYS (with the metabolites 3-ureidopropionate and 3-ureidoisobutyrate) loci. Our study suggests that there may be regulatory pathways of particular relevance to the salivary metabolome. In addition, some of our findings may have clinical significance, such as the utility of the pyrimidine (uracil) degradation metabolites in predicting 5-fluorouracil toxicity and the role of the agmatine pathway metabolites as biomarkers of oral health.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Dihydropyrimidine Dehydrogenase-deficiency; Association; Variants; Agmatine; Disease; Health; Mass
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Quellenangaben Volume: 29, Issue: 5, Pages: 864-875 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Reviewing status Peer reviewed