• Miguel Seral-Cortes, Sergio Sabroso-Lasa, Marcela Gonzalez-Gross, Carlos Quesada-Gonzalez, Peter Stehle, Frederic Gottrand, Ascension Marcos, Ligia Esperanza-Diaz, Yannis Manios, Odysseas Androutsos, Kurt Widhalm, Denes Molnar, Inge Huybrechts, Manon Muntaner, Aline Meirhaeghe, Diego Salazar-Tortosa, Jonatan R Ruiz, Luis Mariano Esteban, Idoia Labayen, Luis A Moreno, and HELENA study group.
• Growth, Exercise, Nutrition and Development (GENUD) Research Group, Faculty of Health Sciences, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, Zaragoza, Spain.
• Eur. J. Clin. Invest. 2023 Dec 1; 53 (12): e14081e14081.

BackgroundHepatic 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.MethodsA 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.ResultsThe 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.ConclusionsConsidering BMI status, both GRSs could contribute as complementary tools to help in the early diagnosis of hepatic damage risk in European adolescents.© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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