Luis A. Moreno, Rosaura Leis, Jesús Alcalá-Fdez, Augusto Anguita-Ruiz, Francisco Jesus Llorente-Cantarero, Azahara I. Rupérez, Concepción M. Aguilera, Gloria Bueno, Esther M González-Gil, Angel Gil, Belén Pastor-Villaescusa, Mercedes Gil-Campos, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, [Anguita-Ruiz,A, González-Gil,EM, Pastor-Villaescusa,B, Gil,Á, Aguilera,CM] Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'José Mataix', Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. Armilla, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Anguita-Ruiz,A, Llorente-Cantarero,FJ, Moreno,LA, Gil-Campos,M, Bueno,G, Leis,R, Aguilera,CM] CIBEROBN (Physiopathology of Obesity and Nutrition Network CB12/03/30038), Institute of Health Carlos III (ISCIII), Madrid, Spain. [González-Gil,EM, Rupérez,AI, Bueno,G] Growth, Exercise, Nutrition and Development (GENUD) Research Group, Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza, Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain. [Llorente-Cantarero,FJ] Department of Specific Didactics, Faculty of Education, University of Córdoba, Córdoba, Spain. [Llorente-Cantarero,FJ, Gil-Campos,M] PAIDI CTS-329, Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain. [Pastor-Villaescusa,B] LMU—Ludwig-Maximilians-University of Munich, Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, University of Munich Medical Center, Munich, Germany. [Alcalá-Fdez,J] Department of Computer Science and Artificial Intelligence, University of Granada,Granada, Spain. [Gil-Campos,M] Unit of Pediatric Endocrinology, Reina Sofia University Hospital, Córdoba, Spain. [Bueno,G] Pediatric Department, Lozano Blesa University Clinical Hospital, University of Zaragoza, Zaragoza, Spain. [Leis,R] Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Pediatric Department, Clinic University Hospital of Santiago, University of Santiago de Compostela, Santiago de Compostela, Spain., This research was supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI1102042, PI1102059, PI1601301 and PI1600871), by the Spanish Ministry of Health, Social and Equality, General Department for Pharmacy and Health Products (EC10-243, EC10-056, EC10-281 and EC10-227), and by the Regional Government of Andalusia ('Plan Andaluz de investigación, desarrollo e innovación (2018), P18-RT-2248') and by the Mapfre Foundation ('Research grants by Ignacio H. de Larramendi 2017'). The authors also acknowledge Instituto de Salud Carlos III for personal funding: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048). The authors also acknowledge the University of Granada 'Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)'.
The authors would like to thank the Spanish children and parents who participated in the study., Polygenetic risk scores (pGRSs) consisting of adult body mass index (BMI) genetic variants have been widely associated with obesity in children populations. The implication of such obesity pGRSs in the development of cardio-metabolic alterations during childhood as well as their utility for the clinical prediction of pubertal obesity outcomes has been barely investigated otherwise. In the present study, we evaluated the utility of an adult BMI predisposing pGRS for the prediction and pharmacological management of obesity in Spanish children, further investigating its implication in the appearance of cardio-metabolic alterations. For that purpose, we counted on genetics data from three well-characterized children populations (composed of 574, 96 and 124 individuals), following both cross-sectional and longitudinal designs, expanding childhood and puberty. As a result, we demonstrated that the pGRS is strongly associated with childhood BMI Z-Score (B = 1.56, SE = 0.27 and p-value = 1.90 × 10−8 ), and that could be used as a good predictor of obesity longitudinal trajectories during puberty. On the other hand, we showed that the pGRS is not associated with cardio-metabolic comorbidities in children and that certain environmental factors interact with the genetic predisposition to the disease. Finally, according to the results derived from a weight-reduction metformin intervention in children with obesity, we discarded the utility of the pGRS as a pharmacogenetics marker of metformin response., Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI1102042 PI1102059 PI1601301 PI1600871, Spanish Ministry of Health, Social and Equality, General Department for Pharmacy and Health Products EC10-243 EC10-056 EC10-281 EC10-227, Regional Government of Andalusia ("Plan Andaluz de investigacion, desarrollo e innovacion (2018)") P18-RT-2248, Mapfre Foundation ("Research grants by Ignacio H. de Larramendi 2017"), Instituto de Salud Carlos III IFI17/00048