Anguita-Ruiz, AugustoGonzález-Gil, Esther M.Rupérez, Azahara I.Llorente-Cantarero, Francisco JesúsPastor-Villaescusa, BelénAlcalá-Fdez, JesúsMoreno, Luis A.Gil, ÁngelGil-Campos, MercedesBueno, GloriaLeis, RosauraAguilera, Concepción M.2022-11-232022-11-232020-06-02Anguita-Ruiz A, González-Gil EM, Rupérez AI, Llorente-Cantarero FJ, Pastor-Villaescusa B, Alcalá-Fdez J, et al. Evaluation of the Predictive Ability, Environmental Regulation and Pharmacogenetics Utility of a BMI-Predisposing Genetic Risk Score during Childhood and Puberty. J Clin Med. 2020 Jun 2;9(6):1705http://hdl.handle.net/10668/4395Polygenetic 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/ObesityChildhood obesityMetabolic syndromeGeneticsGenetic risk scorePharmacogeneticsPredictive abilityGene-environment interactionsPubertyChildhoodSpanish childrenObesidadObesidad pediátricaSíndrome metabólicoGenéticaFarmacogenéticaInteracción gen-ambientePubertadMedical Subject Headings::Persons::Persons::Age Groups::ChildMedical Subject Headings::Persons::Persons::Age Groups::AdultMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Anthropometry::Body Weights and Measures::Body Mass IndexMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity::Pediatric ObesityMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional StudiesMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to DiseaseMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Pharmacology::PharmacogeneticsMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::PubertyMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk FactorsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::Biguanides::MetforminMedical Subject Headings::Geographical Locations::Geographic Locations::Europe::Spainresearch article32498346open access10.3390/jcm90617052077-0383PMC7355743