128019 20241125101144.0 doi 10.1111/eci.14081 sideral 135151 ART-2023-135151 eng Seral-Cortes, Miguel The body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: The HELENA study 2023 Access copy available to the general public Unrestricted Background 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. info:eu-repo/grantAgreement/EUR/FP6/FOOD-CT-2005-007034 info:eu-repo/grantAgreement/EC/H2020/101030971/EU/Human climate adaptation and implications for health/ClimAHealth This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 101030971-ClimAHealth info:eu-repo/grantAgreement/EC/H2020/801586/EU/International Doctoral Programme for Talent Attraction to the Campus of International Excellence of the Ebro Valley/IberusTalent This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 801586-IberusTalent info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 4.4 2023 MEDICINE, GENERAL & INTERNAL 37 / 329 = 0.112 2023 Q1 T1 MEDICINE, RESEARCH & EXPERIMENTAL 57 / 189 = 0.302 2023 Q2 T1 1.27 2023 Biochemistry 2023 Q1 Medicine (miscellaneous) 2023 Q1 Clinical Biochemistry 2023 Q1 9.5 2023 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Sabroso-Lasa, Sergio Gonzalez-Gross, Marcela Quesada-Gonzalez, Carlos Stehle, Peter Gottrand, Frederic Marcos, Ascension Esperanza-Diaz, Ligia Manios, Yannis Androutsos, Odysseas Widhalm, Kurt Molnar, Denes Huybrechts, Inge Muntaner, Manon Meirhaeghe, Aline Salazar-Tortosa, Diego Ruiz, Jonatan R. Esteban, Luis Mariano (orcid)0000-0002-3007-302X Labayen, Idoia Moreno, Luis A. 53, 12 (2023), e14081 [12 pp.] Eur. j. clin. investig. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION 0014-2972 983358 http://zaguan.unizar.es/record/128019/files/texto_completo.pdf Versión publicada 2288072 http://zaguan.unizar.es/record/128019/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:128019 articulos driver 2024-11-22-12:03:56 ARTICLE