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

Gloria Pérez-Gimeno; Miguel Seral-Cortes; Sergio Sabroso-Lasa; Luis Mariano Esteban; Empar Lurbe; Laurent Béghin; Frederic Gottrand; Aline Meirhaeghe; Manon Muntaner; Anthony Kafatos; Dénes Molnár; Catherine Leclercq; Kurt Widhalm; Mathilde Kersting; Esther Nova; Diego F Salazar-Tortosa; Marcela Gonzalez-Gross; Christina Breidenassel; Kathrin Sinningen; Thaïs De Ruyter; Idoia Labayen; Azahara I Rupérez; Gloria Bueno-Lozano; Luis A Moreno

doi:10.3389/fcvm.2023.1118919

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

Front Cardiovasc Med. 2023 Jun 1:10:1118919. doi: 10.3389/fcvm.2023.1118919. eCollection 2023.

Authors

Gloria Pérez-Gimeno^{1

2}, Miguel Seral-Cortes^{1

2}, Sergio Sabroso-Lasa³, Luis Mariano Esteban⁴, Empar Lurbe^{2

5}, Laurent Béghin⁶, Frederic Gottrand⁶, Aline Meirhaeghe⁷, Manon Muntaner⁷, Anthony Kafatos⁸, Dénes Molnár⁹, Catherine Leclercq¹⁰, Kurt Widhalm¹¹, Mathilde Kersting¹², Esther Nova¹³, Diego F Salazar-Tortosa^{14

15}, Marcela Gonzalez-Gross^{2

16}, Christina Breidenassel^{12

16}, Kathrin Sinningen¹⁷, Thaïs De Ruyter¹⁸, Idoia Labayen¹⁹, Azahara I Rupérez¹, Gloria Bueno-Lozano^{1

2}, Luis A Moreno^{1

2}

Affiliations

¹ Growth, Exercise, NUtrition and Development (GENUD), Research Group, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, Zaragoza, Spain.
² Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.
³ Genetic and Molecular Epidemiology Group (GMEG), Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
⁴ Escuela Politécnica de La Almunia, Universidad de Zaragoza, Zaragoza, Spain.
⁵ INCLIVA Biomedical Research Institute, Pediatric Department, Consorcio Hospital General, University of Valencia, Valencia, Spain.
⁶ Université Lille, Inserm, CHU Lille, INFINITE-Institute for Translational Research in Inflammation, Lille, France.
⁷ Risk Factors and Molecular Determinants of Aging-Related Diseases (RID-AGE), Centre Hosp. Univ Lille, Institut Pasteur de Lille, Université de Lille, Lille, France.
⁸ Department of Social Medicine, Preventive Medicine and Nutrition Clinic, University of Crete School of Medicine, Heraklion, Greece.
⁹ Department of Pediatrics, University of Pecs, Pecs, Hungary.
¹⁰ INRAN, National Research Institute for Food and Nutrition, Food and Nutrition Research Centre-Council for Agricultural Research and Economics, Rome, Italy.
¹¹ Division of Clinical Nutrition and Prevention, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
¹² Departement of Nutrition-Human Nutrition, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
¹³ Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN), CSIC, Madrid, Spain.
¹⁴ Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ, United States.
¹⁵ PROFITH 'PROmoting FITness and Health Through Physical Activity' Research Group, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain.
¹⁶ ImFine Research Group, Department of Health and Human Performance, Facultad de Ciencias de la Actividad Física y del Deporte-INEF, Universidad Politécnica de Madrid, Madrid, Spain.
¹⁷ Research Department of Child Nutrition, University Hospital of Pediatrics and Adolescent Medicine, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
¹⁸ Department of Public Health and Primary Care, Ghent University, Ghent, Belgium.
¹⁹ Department of Health Sciences, Institute for Innovation & Sustainable Food Chain Development, Public University of Navarra, Pamplona, Spain.

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.

Keywords: Europe; adolescents; blood pressure; genetic risk score; hypertension; prevention.

© 2023 Pérez-Gimeno, Seral-Cortes, Sabroso-Lasa, Esteban, Lurbe, Béghin, Gottrand, Meirhaeghe, Muntaner, Kafatos, Molnár, Leclercq, Widhalm, Kersting, Nova, Salazar-Tortosa, Gonzalez-Gross, Breidenassel, Sinningen, De Ruyter, Labayen, Rupérez, Bueno-Lozano and Moreno.

Grants and funding

The HELENA Study was financial support of the European Community Sixth RTD Framework Programme (contract FOOD-CT-2005-007034). GP-G, has receiving a predoctoral fellowship from the Government of Aragón. DFS-T was supported by a Marie S. Curie Global Fellowship within the European Union research and innovation framework programme (2014–2020; ClimAHealth: 101030971). MS-C 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. This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project “PI20/00988” and co-funded by the European Union.