Evaluation of the Predictive Ability, Environmental Regulation and Pharmacogenetics Utility of a BMI-Predisposing Genetic Risk Score during Childhood and Puberty
MetadataShow full item record
AuthorAnguita-Ruiz, Augusto; González Gil, Esther M.; Pastor-Villaescusa, Belén; Alcalá Fernández, Jesús; Gil Hernández, Ángel; Aguilera García, Concepción María
ObesityChildhood obesityMetabolic syndromeGeneticsGenetic risk scorePharmacogeneticsPredictive abilityGene-environment interactionsPubertyChildhoodSpanish children
Anguita-Ruiz, A., González-Gil, E. M., Rupérez, A. I., Llorente-Cantarero, F. J., Pastor-Villaescusa, B., Alcalá-Fdez, J., ... & Leis, R. (2020). Evaluation of the Predictive Ability, Environmental Regulation and Pharmacogenetics Utility of a BMI-Predisposing Genetic Risk Score during Childhood and Puberty. Journal of Clinical Medicine, 9(6), 1705. [doi: 10.3390/jcm9061705]
SponsorshipPlan 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
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.