Development of a Genetic Risk Score to predict the risk of overweight and obesity in European adolescents from the HELENA study.


Seral-Cortes M(1), Sabroso-Lasa S(2), De Miguel-Etayo P(3)(4)(5), Gonzalez-Gross M(5)(6)(7), Gesteiro E(7), Molina-Hidalgo C(8), De Henauw S(9), Gottrand F(10), Mavrogianni C(11), Manios Y(11), Plada M(12), Widhalm K(13), Kafatos A(14), Erhardt É(15), Meirhaeghe A(16), Salazar-Tortosa D(17), Ruiz J(18), Moreno LA(3)(4)(5), Esteban LM(19), Labayen I(20).
Author information:
(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. [Email]
(2)Spanish National Cancer Research Centre
(CNIO), Madrid, Spain.
(3)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.
(4)Instituto de Investigación Sanitaria Aragón
(IIS Aragón), Zaragoza, Spain.
(5)Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición
(CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.
(6)Institute of Nutritional and Food Sciences, Nutritional Physiology, University of Bonn, Bonn, Germany.
(7)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.
(8)EFFECTS 262 Department of Medical Physiology, School of Medicine, University of Granada, 18071, Granada, Spain.
(9)Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
(10)Faculty of Medicine, University Lille, Lille, France.
(11)Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
(12)University of Crete School of Medicine, Crete, Greece.
(13)Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria and Austrian Academic Institute for Clinical Nutrition, Vienna, Austria.
(14)Faculty of Medicine, University of Crete, Crete, Greece.
(15)Department of Pediatrics, Medical School, University of Pécs, Pecs, Hungary.
(16)UMR1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Centre Hosp. Univ Lille, Institut Pasteur de Lille, Université de Lille, Lille, France.
(17)Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ, USA.
(18)Departmento de Actividad Física y Deporte, Faculty of Sport Sciences, Universidad de Granada, Granada, Spain.
(19)Escuela Politécnica de La Almunia, Universidad de Zaragoza, Zaragoza, Spain.
(20)Department of Health Sciences, Public University of Navarra, Pamplona, Spain.


Obesity is the result of interactions between genes and environmental factors. Since monogenic etiology is only known in some obesity-related genes, a genetic risk score (GRS) could be useful to determine the genetic predisposition to obesity. Therefore, the aim of our study was to build a GRS able to predict genetic predisposition to overweight and obesity in European adolescents. A total of 1069 adolescents (51.3% female), aged 11-19 years participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were genotyped. The sample was divided in non-overweight (non-OW) and overweight/obesity (OW/OB). From 611 single nucleotide polymorphisms (SNP) available, a first screening of 104 SNPs univariately associated with obesity (p < 0.20) was established selecting 21 significant SNPs (p < 0.05) in the multivariate model. Unweighted GRS (uGRS) was calculated by summing the number of risk alleles and weighted GRS (wGRS) by multiplying the risk alleles to each estimated coefficient. The area under curve (AUC) was calculated in uGRS (0.723) and wGRS (0.734) using tenfold internal cross-validation. Both uGRS and wGRS were significantly associated with body mass index (BMI) (p < .001). Both GRSs could potentially be considered as useful genetic tools to evaluate individual's predisposition to overweight/obesity in European adolescents.