The body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: The HELENA study
Seral-Cortes, Miguel ; 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 ; Labayen, Idoia ; Moreno, Luis A. ;
Resumen: 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.
Idioma: Inglés
DOI: 10.1111/eci.14081
Año: 2023
Publicado en: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION 53, 12 (2023), e14081 [12 pp.]
ISSN: 0014-2972
Factor impacto JCR: 4.4 (2023)
Categ. JCR: MEDICINE, GENERAL & INTERNAL rank: 36 / 325 = 0.111 (2023) - Q1 - T1
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 57 / 189 = 0.302 (2023) - Q2 - T1
Factor impacto CITESCORE: 9.5 - Clinical Biochemistry (Q1) - Biochemistry (Q1)
Factor impacto SCIMAGO: 1.27 - Biochemistry (Q1) - Medicine (miscellaneous) (Q1) - Clinical Biochemistry (Q1)
Financiación: info:eu-repo/grantAgreement/EUR/FP6/FOOD-CT-2005-007034
Financiación: info:eu-repo/grantAgreement/EC/H2020/101030971/EU/Human climate adaptation and implications for health/ClimAHealth
Financiación: 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
Tipo y forma: Artículo (Versión definitiva)
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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.
Idioma: Inglés
DOI: 10.1111/eci.14081
Año: 2023
Publicado en: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION 53, 12 (2023), e14081 [12 pp.]
ISSN: 0014-2972
Factor impacto JCR: 4.4 (2023)
Categ. JCR: MEDICINE, GENERAL & INTERNAL rank: 36 / 325 = 0.111 (2023) - Q1 - T1
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 57 / 189 = 0.302 (2023) - Q2 - T1
Factor impacto CITESCORE: 9.5 - Clinical Biochemistry (Q1) - Biochemistry (Q1)
Factor impacto SCIMAGO: 1.27 - Biochemistry (Q1) - Medicine (miscellaneous) (Q1) - Clinical Biochemistry (Q1)
Financiación: info:eu-repo/grantAgreement/EUR/FP6/FOOD-CT-2005-007034
Financiación: info:eu-repo/grantAgreement/EC/H2020/101030971/EU/Human climate adaptation and implications for health/ClimAHealth
Financiación: 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
Tipo y forma: Artículo (Versión definitiva)
Debe reconocer adecuadamente la autoría, proporcionar un enlace a la licencia e indicar si se han realizado cambios. Puede hacerlo de cualquier manera razonable, pero no de una manera que sugiera que tiene el apoyo del licenciador o lo recibe por el uso que hace. No puede utilizar el material para una finalidad comercial. Si remezcla, transforma o crea a partir del material, no puede difundir el material modificado.Exportado de SIDERAL (2024-07-31-09:53:01)
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Registro creado el 2023-10-27, última modificación el 2024-07-31