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Title

Development of a genetic risk score to predict the risk of hypertension in European adolescents from the HELENA study

AuthorsPérez-Gimeno, Gloria; Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; Esteban, Luis Mariano; Lurbe, Empar; Béghin, Laurent; Molnár, Dénes; Leclercq, Catherine; Widhalm, Kurt; Kersting, Mathilde; Nova, Esther CSIC ORCID ; Salazar-Tortosa, Diego; González-Gross, Marcela CSIC ORCID; Breidenassel, Christina; Sinningen, Kathrin; De Ruyter, Thaïs; Labayen, Idoia; Rupérez, Azahara I.; Bueno, Gloria; Moreno, Luis A.
KeywordsEurope
Adolescents
Blood pressure
Genetic risk score
Hypertension
Prevention
Issue Date2023
PublisherFrontiers Media
CitationFrontiers in Cardiovascular Medicine 10: 1118919 (2023)
Abstract[Introduction]: From genome wide association study (GWAS) a large number of single nucleotide polymorphisms (SNPs) have previously been associated with blood pressure (BP) levels. A combination of SNPs, forming a genetic risk score (GRS) could be considered as a useful genetic tool to identify individuals at risk of developing hypertension from early stages in life. Therefore, the aim of our study was to build a GRS being able to predict the genetic predisposition to hypertension (HTN) in European adolescents.
[Methods]: Data were extracted from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study. A total of 869 adolescents (53% female), aged 12.5-17.5, with complete genetic and BP information were included. The sample was divided into altered (≥130 mmHg for systolic and/or ≥80 mmHg for diastolic) or normal BP. Based on the literature, a total of 1.534 SNPs from 57 candidate genes related with BP were selected from the HELENA GWAS database.
[Results]: From 1,534 SNPs available, An initial screening of SNPs univariately associated with HTN (p < 0.10) was established, to finally obtain a number of 16 SNPs significantly associated with HTN (p < 0.05) in the multivariate model. The unweighted GRS (uGRS) and weighted GRS (wGRS) were estimated. To validate the GRSs, the area under the curve (AUC) was explored using ten-fold internal cross-validation for uGRS (0.802) and wGRS (0.777). Further covariates of interest were added to the analyses, obtaining a higher predictive ability (AUC values of uGRS: 0.879; wGRS: 0.881 for BMI z-score). Furthermore, the differences between AUCs obtained with and without the addition of covariates were statistically significant (p < 0.05).
[Conclusions]: Both GRSs, the uGRS and wGRS, could be useful to evaluate the predisposition to hypertension in European adolescents.
Publisher version (URL)https://doi.org/10.3389/fcvm.2023.1118919
URIhttp://hdl.handle.net/10261/341162
DOI10.3389/fcvm.2023.1118919
E-ISSN2297-055X
Appears in Collections:(ICTAN) Artículos




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