Urinary metabolite quantitative trait loci in children and their interaction with dietary factors

Calvo Serra, Beatriz; Maitre, Léa; Lau, Chung-Ho E.; Siskos, Alexandros P.; Gützkow, Kristine B.; Andrušaitytė, Sandra; Casas Sanahuja, Maribel; Cadiou, Solène; Chatzi, Leda; González, Juan Ramón; Gražulevičienė, Regina; McEachan, Rosemary R.C.; Slama, Rémy; Vafeiadi, Marina, 1983-; Wright, John; Coen, Muireann; Vrijheid, Martine; Keun, Hector C.; Escaramís, Geòrgia; Bustamante Pineda, Mariona

Urinary metabolite quantitative trait loci in children and their interaction with dietary factors

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dc.contributor.author Calvo Serra, Beatriz
dc.contributor.author Maitre, Léa
dc.contributor.author Lau, Chung-Ho E.
dc.contributor.author Siskos, Alexandros P.
dc.contributor.author Gützkow, Kristine B.
dc.contributor.author Andrušaitytė, Sandra
dc.contributor.author Casas Sanahuja, Maribel
dc.contributor.author Cadiou, Solène
dc.contributor.author Chatzi, Leda
dc.contributor.author González, Juan Ramón
dc.contributor.author Gražulevičienė, Regina
dc.contributor.author McEachan, Rosemary R.C.
dc.contributor.author Slama, Rémy
dc.contributor.author Vafeiadi, Marina, 1983-
dc.contributor.author Wright, John
dc.contributor.author Coen, Muireann
dc.contributor.author Vrijheid, Martine
dc.contributor.author Keun, Hector C.
dc.contributor.author Escaramís, Geòrgia
dc.contributor.author Bustamante Pineda, Mariona
dc.date.accessioned 2021-07-22T06:29:37Z
dc.date.issued 2021
dc.description.abstract Human metabolism is influenced by genetic and environmental factors. Previous studies have identified over 23 loci associated with more than 26 urine metabolites levels in adults, which are known as urinary metabolite quantitative trait loci (metabQTLs). The aim of the present study is the identification for the first time of urinary metabQTLs in children and their interaction with dietary patterns. Association between genome-wide genotyping data and 44 urine metabolite levels measured by proton nuclear magnetic resonance spectroscopy was tested in 996 children from the Human Early Life Exposome project. Twelve statistically significant urine metabQTLs were identified, involving 11 unique loci and 10 different metabolites. Comparison with previous findings in adults revealed that six metabQTLs were already known, and one had been described in serum and three were involved the same locus as other reported metabQTLs but had different urinary metabolites. The remaining two metabQTLs represent novel urine metabolite-locus associations, which are reported for the first time in this study [single nucleotide polymorphism (SNP) rs12575496 for taurine, and the missense SNP rs2274870 for 3-hydroxyisobutyrate]. Moreover, it was found that urinary taurine levels were affected by the combined action of genetic variation and dietary patterns of meat intake as well as by the interaction of this SNP with beverage intake dietary patterns. Overall, we identified 12 urinary metabQTLs in children, including two novel associations. While a substantial part of the identified loci affected urinary metabolite levels both in children and in adults, the metabQTL for taurine seemed to be specific to children and interacted with dietary patterns.
dc.description.sponsorship This work was supported by the European Community’s Seventh Framework Programme (FP7/2007-206) [grant agreement no 308333 (HELIX project)]; and the H2020-EU.3.1.2. - Preventing Disease Programme [grant agreement no 874583 (ATHLETE project)]. The genotyping was supported by Instituto de Salud Carlos III [PI17/01225]; and co-funded by European Union (ERDF, “A way to make Europe”) and the Centro Nacional de Genotipado-CEGEN [PRB2-ISCIII]. BiB received core infrastructure funding from the Wellcome Trust [WT101597MA]; and a joint grant from the UK Medical Research Council and Economic and Social Science Research Council [MR/N024397/1]. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology [6-04-2014_31V-66]. The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The Rhea project was financially supported by European projects [EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX], and the Greek Ministry of Health [Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011-2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-15]. We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program [CEX2018-000806-S], and support from the Generalitat de Catalunya through the CERCA Program.
dc.format.mimetype application/pdf
dc.identifier.citation Calvo-Serra B, Maitre L, Lau CE, Siskos AP, Gützkow KB, Andrušaitytė S, Casas M, Cadiou S, Chatzi L, González JR, Grazuleviciene R, McEachan R, Slama R, Vafeiadi M, Wright J, Coen M, Vrijheid M, Keun HC, Escaramís G, Bustamante M. Urinary metabolite quantitative trait loci in children and their interaction with dietary factors. Hum Mol Genet. 2021;29(23):3830-44. DOI: 10.1093/hmg/ddaa257
dc.identifier.doi http://dx.doi.org/10.1093/hmg/ddaa257
dc.identifier.issn 0964-6906
dc.identifier.uri http://hdl.handle.net/10230/48273
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof Hum Mol Genet. 2021;29(23):3830-44
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/211250
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/226285
dc.rights © Oxford University Press. This is a pre-copyedited, author-produced version of an article accepted for publication in Human molecular genetics following peer review. The version of record Calvo-Serra B, Maitre L, Lau CE, Siskos AP, Gützkow KB, Andrušaitytė S, Casas M, Cadiou S, Chatzi L, González JR, Grazuleviciene R, McEachan R, Slama R, Vafeiadi M, Wright J, Coen M, Vrijheid M, Keun HC, Escaramís G, Bustamante M. Urinary metabolite quantitative trait loci in children and their interaction with dietary factors. Hum Mol Genet. 2021;29(23):3830-44. DOI: 10.1093/hmg/ddaa257 is available online at: http://dx.doi.org/10.1093/hmg/ddaa257
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.keyword Adult
dc.subject.keyword Child
dc.subject.keyword Single nucleotide polymorphism
dc.subject.keyword Urinary tract
dc.subject.keyword Urine
dc.subject.keyword Metabolites
dc.subject.keyword Quantitative trait loci
dc.title Urinary metabolite quantitative trait loci in children and their interaction with dietary factors
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/acceptedVersion

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