The body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: the HELENA study

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dc.contributor.authorSeral-Cortes, Miguel
dc.contributor.authorSabroso-Lasa, Sergio
dc.contributor.authorGonzález Gross, Marcela
dc.contributor.authorQuesada-González, Carlos
dc.contributor.authorStehle, Peter
dc.contributor.authorGottrand, Frédéric
dc.contributor.authorMarcos, Ascensión
dc.contributor.authorDiaz, Ligia Esperanza
dc.contributor.authorManios, Yannis
dc.contributor.authorAndroutsos, Odysseas
dc.contributor.authorWidhalm, Kurt
dc.contributor.authorMolnár, Dénes
dc.contributor.authorHuybrechts, Inge
dc.contributor.authorMuntaner, Manon
dc.contributor.authorMeirhaeghe, Aline
dc.contributor.authorSalazar-Tortosa, Diego
dc.contributor.authorRuiz, Jonatan R.
dc.contributor.authorEsteban, Luis Mariano
dc.contributor.authorLabayen Goñi, Idoia
dc.contributor.authorMoreno, Luis A.
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2023-10-26T18:13:36Z
dc.date.available2023-10-26T18:13:36Z
dc.date.issued2023
dc.date.updated2023-10-26T17:31:38Z
dc.description.abstractBackground: Hepatic disorders are often complex and multifactorial, modulated by genetic and environmental determinants. During the last years, the hepatic disease has been progressively established from early stages in life. The use of genetic risk scores (GRS) to predict the genetic susceptibility to a particular phenotype among youth has gained interest in recent years. Moreover, the alanine aminotransferase (ALT) blood biomarker is often considered as hepatic screening tool, in combination with imaging techniques. The aim of the present study was to develop an ALT-specific GRS to help in the evaluation of hepatic damage risk in European adolescents. Methods: A total of 972 adolescents (51.3% females), aged 12.5¿17.5 years, from the Healthy Lifestyle in Europe by Nutrition in Adolescence study were included in the analyses. The sample incorporated adolescents in all body mass index (BMI) categories and was divided considering healthy/unhealthy ALT levels, using sex-specific cut-off points. From 1212 a priori ALT-related single nucleotide polymorphisms (SNPs) extracted from candidate gene selection, a first screening of 234 SNPs univariately associated was established, selecting seven significant SNPs (p <.05) in the multivariate model. An unweighted GRS (uGRS) was developed by summing the number of reference alleles, and a weighted GRS (wGRS), by multiplying each allele to its estimated coefficient. Results: The uGRS and wGRS were significantly associated with ALT (p <.001). The area under curve was obtained integrating BMI as clinical factor, improving the predictive ability for uGRS (.7039) and wGRS (.7035), using 10-fold internal cross-validation. Conclusions: Considering BMI status, both GRSs could contribute as complementary tools to help in the early diagnosis of hepatic damage risk in European adolescents.en
dc.description.sponsorshipThis work was supported by the European Community Sixth RTD Framework Programme (contract FOOD-CT-2005-007034) The data for this study were gathered under the auspices of the HELENA project (http://www.helenastudy.com/), and further analysis was additionally supported by the Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn). Miguel Seral-Cortes, the corresponding author, has received funding from the Iberus Talent Pre-doctoral fellowships 2018, under the European Union's H2020 research and innovation programme under Marie Sklodowska-Curie grant agreement No 801586. Diego F. Salazar-Tortosa was supported by a Marie S. Curie Global Fellowship within the European Union research and innovation framework programme (2014–2020; ClimAHealth: 101030971).en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSeral-Cortes, M., Sabroso-Lasa, S., Gonzalez-Gross, M., Quesada-Gonzalez, C., Stehle, P., Gottrand, F., Marcos, A., Esperanza-Diaz, L., Manios, Y., Androutsos, O., Widhalm, K., Molnar, D., Huybrechts, I., Muntaner, M., Meirhaeghe, A., Salazar-Tortosa, D., Ruiz, J. R., Esteban, L. M., Labayen, I., Moreno, L. A. (2023) The body mass index increases the genetic risk scores¿ ability to predict risk of hepatic damage in European adolescents: the HELENA study. European Journal of Clinical Investigation, 1-12. https://doi.org/10.1111/eci.14081.en
dc.identifier.doi10.1111/eci.14081
dc.identifier.issn0014-2972
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/46654
dc.language.isoengen
dc.publisherWileyen
dc.relation.ispartofEuropean Journal of Clinical Investigation, 2023en
dc.relation.projectIDinfo:eu-repo/grantAgreement/European Commission/Horizon 2020 Framework Programme/801586/
dc.relation.projectIDinfo:eu-repo/grantAgreement/European Commission/Horizon 2020 Framework Programme/101030971/
dc.relation.publisherversionhttps://doi.org/10.1111/eci.14081
dc.rights© 2023 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial- NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectALT levelsen
dc.subjectBMI and adolescentsen
dc.subjectGRSen
dc.subjectHepatic disordersen
dc.subjectSingle nucleotide polymorphismen
dc.titleThe body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: the HELENA studyen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationb36e2b1d-3088-4089-806e-fd3040e9583a
relation.isAuthorOfPublication.latestForDiscoveryb36e2b1d-3088-4089-806e-fd3040e9583a

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