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Beyond the FTO Gene: Environmental and Behavioural Factors Associated with BMI and Overweight in Spanish Adolescents

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Open AccessArticle Beyond the FTO Gene: Environmental and Behavioural Factors Associated with BMI and Overweight in Spanish Adolescents by Luciana Margara Luciana Margara Scilit Preprints.org Google Scholar 1, Inés Piñas-Bonilla Inés Piñas-Bonilla Scilit Preprints.org Google Scholar 2, Pablo Abián Pablo Abián Scilit Preprints.org Google Scholar 3, Alfredo Bravo-Sánchez Alfredo Bravo-Sánchez Scilit Preprints.org Google Scholar 4, David Ortiz-Sánchez David Ortiz-Sánchez Scilit Preprints.org Google Scholar 1, María Ramírez-delaCruz María Ramírez-delaCruz Scilit Preprints.org Google Scholar 1, Paula Esteban-García Paula Esteban-García Scilit Preprints.org Google Scholar 1, Javier Portillo Javier Portillo Scilit Preprints.org Google Scholar 1, Carlos Ramírez Carlos Ramírez Scilit Preprints.org Google Scholar 1 and Javier Abián-Vicén Javier Abián-Vicén Scilit Preprints.org Google Scholar Javier Abián-Vicén is a graduate and Doctor in Physical Activity and Sports Sciences and a in from [...] Read more 1,* 1 Performance and Sport Rehabilitation Laboratory, Faculty of Sports Sciences, University of Castilla-La Mancha, 45071 Toledo, Spain 2 Faculty of Medicine, University of Extremadura, 06006 Badajoz, Spain 3 Department of Biomedical Sciences, Area of Physical and Sports Education, Faculty of Medicine and Health Sciences, Universidad de Alcalá, 28871 Alcalá de Henares, Spain 4 Faculty of Health Sciences, Universidad Francisco de Vitoria, 28223 Pozuelo de Alarcón, Spain * Author to whom correspondence should be addressed. Children 2026, 13(6), 782; https://doi.org/10.3390/children13060782 (registering DOI) Submission received: 7 May 2026 / Revised: 30 May 2026 / Accepted: 1 June 2026 / Published: 4 June 2026 Highlights What are the main findings? The FTO rs9939609 polymorphism was not associated with BMI, weight status, or lifestyle-related variables in Spanish adolescents, suggesting a limited role of this genetic factor during this developmental stage. Environmental and behavioural factors, particularly regular breakfast consumption, showed a significant association with lower overweight prevalence, while notable sex differences were observed in physical fitness and activity levels. What are the implications of the main findings? Preventive strategies targeting adolescent overweight should prioritize modifiable lifestyle behaviours, especially the promotion of regular breakfast consumption and increased physical activity. Public health interventions should incorporate sex-specific approaches, acknowledging the lower physical activity and fitness levels observed in girls, to enhance the effectiveness of obesity prevention programmes in adolescence. Abstract Background/objectives: Obesity is a multifactorial condition influenced by interactions between genetic susceptibility and environmental factors. The fat mass and obesity-associated ( FTO) gene has been widely linked to obesity risk, particularly the rs9939609 polymorphism, which is associated with higher body mass index (BMI) and adiposity. However, evidence in adolescents remains inconsistent, and lifestyle factors such as physical activity and diet may modify genetic risk. The objectives of this study were: (i) to examine the influence of environmental, genetic, physical activity, and dietary factors on the BMI and overweight-related variables of adolescents, and (ii) to assess the impact of the rs9939609 polymorphism in the FTO gene on these variables. Methods: A cross-sectional study was conducted involving 206 adolescents aged 12 to 16 years. Body mass index (BMI), physical fitness, physical activity levels, adherence to the Mediterranean diet, mobile phone usage, and FTO rs9939609 genotyping from buccal swabs were collected. Results: No significant associations were found between the FTO genotype and BMI, or with physical activity, mobile phone usage and dietary habits. Boys showed higher physical fitness and physical activity levels than girls ( p 85% overweight, and >95% obese [ 22]. BMI percentiles are widely used in epidemiological studies involving adolescents due to their practicality, accessibility, and established association with overweight and obesity risk [ 23]. 2.2.2. International Physical Activity Questionnaire (IPAQ) The short version of the IPAQ (9 items) was used to assess physical activity related to aerobic capacity in adolescents. This version accounts for physical activity lasting at least 10 min, including leisure-time activities, household tasks, work-related activities, and active transportation over the past seven days. Physical activity levels are classified based on weekly energy expenditure, expressed in metabolic equivalent tasks (MET) minutes/week, where one MET represents resting energy expenditure. A MET score is calculated for walking, moderate activity, and vigorous activity (3.3, 4.0, and 8.0 MET min/week, respectively), and a total index is obtained by summing the MET min/week for each intensity level of physical activity [ 24]. Numerous review studies support the IPAQ’s high level of validity [ 25, 26]. 2.2.3. Questionnaire for Assessing Adherence to the Mediterranean Diet in Children and Adolescents (KIDMED) The KIDMED questionnaire (Mediterranean Diet Quality Index) is a tool used to evaluate adherence to the Mediterranean diet, nutritional status, and overall diet quality in children and adolescents [ 15]. Participants completed a seven-day food diary, covering both weekdays and the full weekend. The assessment included a 16-item Mediterranean Diet Quality Index, a 169-item quantitative food frequency questionnaire, and a general questionnaire addressing socioeconomic, demographic, and lifestyle factors. Scores were categorised into three levels of adherence to the Mediterranean diet: low (≤1), moderate (2–4), and high (≥5). In addition, one specific item from the KIDMED questionnaire—whether or not adolescents ate breakfast—was analysed separately, as several studies have identified an association between breakfast skipping and an increased risk of overweight and obesity in adolescents [ 27, 28]. Upon completion of data collection, the information was analysed using a nutrition software programme specifically designed for the Mediterranean diet by the Centre for Higher Education in Nutrition and Dietetics (CESNID; PCN Cesnid 1.0, Barcelona, Spain). 2.2.4. Mobile-Related Experiences Questionnaire (CERM) The CERM is a questionnaire addressing experiences related to mobile phone use. It consists of 10 items rated on a four-point Likert scale, where 1 corresponds to “almost never” and 4 to “almost always” [ 29]. The questionnaire demonstrates good overall reliability and evaluates two factors: the presence of conflicts, and the communicational and emotional use of mobile phones and social networks among young people [ 30]. 2.2.5. Physical Fitness (ALPHA-Fitness) Several tests from the ALPHA-Fitness battery were conducted; this is a standardised set of physical assessments designed to measure health-related physical fitness in children and adolescents aged 6 to 18 years [ 31]. The tests performed in our study were as follows: Handgrip Strength: Measured using a manual dynamometer (TKK 5401 Grip D, Takei, Tokyo, Japan). During the test, students were instructed to squeeze the dynamometer slowly and steadily for 3 to 5 s. Two trials were performed alternately with both hands, recording the highest value obtained for each hand. Medicine Ball Throw: Participants threw a 2 kg medicine ball overhead as far as possible using trunk and upper limb extension and flexion. Two attempts were made per student, with the distance of each throw recorded; the longest distance was used for analysis. Standing Long Jump: The student stood behind a marked line on the floor with feet together and performed a maximal jump, landing evenly on both feet. Any unbalanced landing was considered a null attempt. Each student performed two attempts, with the distance measured in centimetres using a tape measure; the longest jump was used for subsequent analysis. Cardiorespiratory Capacity: Assessed via the Course-Navette test (20-m shuttle run). Participants ran back and forth over a 20-m course, keeping pace with audio beeps starting at 8.5 km/h and increasing by 0.5 km/h each minute. The test ended when a participant stopped due to fatigue or failed to reach the line before the beep. The time recorded for each participant was noted. 2.2.6. Genetics Genomic DNA was obtained from buccal epithelial cells using a cotton swab according to a previously described protocol [ 32], and genotyping was performed in a certified genetics laboratory. To minimize the risk of contamination, standard recommendations for molecular genetics laboratories were strictly applied, including the use of separate physically isolated areas for each procedure, such as sample handling and DNA extraction. Following collection, the samples were stored at 4 °C and subsequently transported to the laboratory. Upon arrival, genomic DNA extraction was carried out automatically using the QIACube system (QIAGEN, Venlo, The Netherlands) to achieve a final DNA concentration of at least 25 ng/mL. The resulting solution was subsequently stored at −20 °C until genotyping analysis, which was carried out within one week after sample receipt at the laboratory. During genotyping, the rs9939609 polymorphism of the FTO gene (Fat Mass and Obesity-Associated protein), linked to the likelihood of excess adiposity, was analysed. All samples for which genotype determination was inconclusive were reanalyzed. In addition, reference samples, including internal controls, blank samples, and negative controls, together with continuous contamination monitoring, were incorporated throughout every stage of the procedure. Results were analysed using the 7500 v 2.0.5 software (Applied Biosystems, Foster City, CA, USA). The genotyping success rate for this sample was 100%. 2.3. Statistical Analysis Statistical analyses were conducted using IBM SPSS Statistics version 28.0 (SPSS Inc., Chicago, IL, USA). Categorical variables are reported as absolute frequencies and percentages, whereas continuous variables are expressed as mean ± standard deviation. The distribution normality of continuous variables was evaluated using the Kolmogorov–Smirnov test, with all variables showing a parametric distribution ( p > 0.05). The Chi-square test (χ 2) was used to verify that genotype frequencies conformed to the Hardy–Weinberg equilibrium (HWE). The χ 2 test was also applied to determine whether the genotype frequency in the study sample differed from that recorded in ethnically matched controls from the “1000 Genomes Database” [ 33], and to examine the association between breakfast habits and groups defined by BMI percentiles (normal weight, overweight, and obesity). A two-way ANOVA (3 × 2) was conducted to determine the main effects of genotype and sex on the physical variables and questionnaire outcomes analysed. The ANOVA factors were genotype (AA, AT, and TT) and sex (boys vs. girls). When significant main effects were detected in the ANOVA, the Bonferroni correction was applied as a post-hoc test. 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Group Genotype Frequency Allele Frequency AA AT TT A T All ( n = 206) 24 (11.7) 110 (53.3) 72 (35.0) 158 (38.3) 254 (61.7) Boys ( n = 119) 16 (13.4) 63 (52.9) 40 (33.6) 95 (39.9) 143 (60.1) Girls ( n = 87) 8 (9.2) 47 (54.0) 32 (36.8) 63 (36.2) 111 (63.8) 1000 genome database; European 16.8 48.4 34.8 41.0 59.0 Table 2. Association between FTO gene genotype and groups classified by body mass index (BMI) percentile. [number (frequency)]. Table 2. Association between FTO gene genotype and groups classified by body mass index (BMI) percentile. [number (frequency)]. Group Genotype Frequency AA AT TT Total Normal 19 (11.5) 87 (52.7) 59 (35.8) 165 (100.0) Overweight 3 (9.7) 17 (54.8) 11 (35.5) 31 (100.0) Obesity 2 (20.0) 6 (60.0) 2 (20.0) 10 (100.0) All 24 (11.7) 110 (53.4) 72 (35.0) 206 (100.0) Table 3. Physical fitness assessments (mean ± SD) from the ALPHA-Fitness battery stratified by FTO rs9939609 genotype (AA, AT, TT) and by sex in the sample of 206 schoolchildren. Results of two-way ANOVA (sex × genotype) are included. Table 3. Physical fitness assessments (mean ± SD) from the ALPHA-Fitness battery stratified by FTO rs9939609 genotype (AA, AT, TT) and by sex in the sample of 206 schoolchildren. Results of two-way ANOVA (sex × genotype) are included. AA AT TT Sex × Genotype Sex Genotype Standing long jump (m) Boys ୧.୬୫ ବ୍ଦ ୦.୩୩ ୧.୭୨ ବ୍ଦ ୦.୩୧ ୧.୬୮ ବ୍ଦ ୦.୩୧ 0.832 0.003 0.463 Girls ୧.୩୮ ବ୍ଦ ୦.୧୭ ୧.୫୪ ବ୍ଦ ୦.୨୮ ୧.୫୧ ବ୍ଦ ୦.୧୪ Medicine ball throw (m) Boys ୪.୮୧ ବ୍ଦ ୧.୦୭ ୫.୧୬ ବ୍ଦ ୧.୦୧ ୫.୧୧ ବ୍ଦ ୧.୩୦ 0.140 0.039 0.529 Girls ୫.୧୨ ବ୍ଦ ୨.୦୬ ୪.୩୪ ବ୍ଦ ୦.୮୨ ୪.୦୬ ବ୍ଦ ୧.୦୪ Handgrip strength right (kg) Boys ୨୫.୯ ବ୍ଦ ୭.୮ ୨୯.୨ ବ୍ଦ ୮.୩ ୨୭.୩ ବ୍ଦ ୭.୬ 0.899 <0.001 0.110 Girls ୨୦.୭ ବ୍ଦ ୨.୭ ୨୩.୪ ବ୍ଦ ୩.୮ ୨୨.୪ ବ୍ଦ ୪.୩ Handgrip strength left (kg) Boys ୨୨.୯ ବ୍ଦ ୫.୮ ୨୬.୭ ବ୍ଦ ୭.୧ ୨୪.୩ ବ୍ଦ ୬.୫ 0.591 <0.001 0.081 Girls ୧୯.୩ ବ୍ଦ ୩.୬ ୨୧.୩ ବ୍ଦ ୩.୯ ୨୦.୫ ବ୍ଦ ୩.୪ Course navette (min) Boys ୬.୬୦ ବ୍ଦ ୧.୩୯ ୬.୨୦ ବ୍ଦ ୨.୦୧ ୫.୬୬ ବ୍ଦ ୨.୨୬ 0.708 <0.001 0.693 Girls ୩.୯୦ ବ୍ଦ ୨.୫୬ ୪.୦୪ ବ୍ଦ ୧.୪୧ ୩.୯୫ ବ୍ଦ ୧.୦୮ Table 4. Mean ± SD scores for Body Mass Index (BMI), the International Physical Activity Questionnaire (IPAQ), the Mobile-Related Experiences Questionnaire (CERM), and the Mediterranean Diet Quality Index for children and adolescents (KIDMED), stratified by FTO rs9939609 genotype (AA, AT, TT) and by sex in the sample of 206 schoolchildren. Table 4. Mean ± SD scores for Body Mass Index (BMI), the International Physical Activity Questionnaire (IPAQ), the Mobile-Related Experiences Questionnaire (CERM), and the Mediterranean Diet Quality Index for children and adolescents (KIDMED), stratified by FTO rs9939609 genotype (AA, AT, TT) and by sex in the sample of 206 schoolchildren. AA AT TT Sex × Genotype Sex Genotype BMI (Kg/m 2) Boys ୨୦.୯ ବ୍ଦ ୨.୭ ୨୦.୫ ବ୍ଦ ୩.୬ ୨୦.୫ ବ୍ଦ ୩.୫ 0.872 0.998 0.753 Girls ୨୧.୦ ବ୍ଦ ୩.୭ ୨୦.୭ ବ୍ଦ ୩.୩ ୨୦.୨ ବ୍ଦ ୨.୫ IPAQ (score) Boys ୫୨୩୬ ବ୍ଦ ୨୮୪୮ ୪୯୭୧ ବ୍ଦ ୩୩୪୩ ୫୩୮୭ ବ୍ଦ ୪୦୫୩ 0.777 <0.001 0.982 Girls ୩୦୭୯ ବ୍ଦ ୨୦୩୭ ୩୨୩୯ ବ୍ଦ ୨୧୬୯ ୩୦୦୧ ବ୍ଦ ୨୨୦୧ CERM (score) Boys ୧୫.୬ ବ୍ଦ ୨.୯ ୧୫.୯ ବ୍ଦ ୩.୬ ୧୬.୪ ବ୍ଦ ୩.୧ 0.770 0.121 0.635 Girls ୧୬.୩ ବ୍ଦ ୪.୭ ୧୭.୫ ବ୍ଦ ୪.୪ ୧୭.୩ ବ୍ଦ ୪.୮ KIDMED (score) Boys ୫.୬୩ ବ୍ଦ ୨.୩୧ ୫.୫୬ ବ୍ଦ ୨.୪୦ ୫.୦୩ ବ୍ଦ ୨.୩୧ 0.253 0.453 0.752 Girls ୫.୩୮ ବ୍ଦ ୪.୦୩ ୪.୫୫ ବ୍ଦ ୨.୭୫ ୫.୨୮ ବ୍ଦ ୨.୧୩ Table 5. Association between breakfast consumption and groups defined by body mass index (BMI) percentiles. Table 5. Association between breakfast consumption and groups defined by body mass index (BMI) percentiles. BMI Breakfast No Yes Total Normal 43 (26.1) 122 (73.9) 165 (100.0) Overweight and Obesity 20 (48.8) 21 (51.2) 41 (100.0) All 63 (30.6) 143 (69.4) 206 (100.0) Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Share and Cite MDPI and ACS Style Margara, L.; Piñas-Bonilla, I.; Abián, P.; Bravo-Sánchez, A.; Ortiz-Sánchez, D.; Ramírez-delaCruz, M.; Esteban-García, P.; Portillo, J.; Ramírez, C.; Abián-Vicén, J. Beyond the FTO Gene: Environmental and Behavioural Factors Associated with BMI and Overweight in Spanish Adolescents. Children 2026, 13, 782. https://doi.org/10.3390/children13060782 AMA Style Margara L, Piñas-Bonilla I, Abián P, Bravo-Sánchez A, Ortiz-Sánchez D, Ramírez-delaCruz M, Esteban-García P, Portillo J, Ramírez C, Abián-Vicén J. Beyond the FTO Gene: Environmental and Behavioural Factors Associated with BMI and Overweight in Spanish Adolescents. Children. 2026; 13(6):782. https://doi.org/10.3390/children13060782 Chicago/Turabian Style Margara, Luciana, Inés Piñas-Bonilla, Pablo Abián, Alfredo Bravo-Sánchez, David Ortiz-Sánchez, María Ramírez-delaCruz, Paula Esteban-García, Javier Portillo, Carlos Ramírez, and Javier Abián-Vicén. 2026. "Beyond the FTO Gene: Environmental and Behavioural Factors Associated with BMI and Overweight in Spanish Adolescents" Children 13, no. 6: 782. https://doi.org/10.3390/children13060782 APA Style Margara, L., Piñas-Bonilla, I., Abián, P., Bravo-Sánchez, A., Ortiz-Sánchez, D., Ramírez-delaCruz, M., Esteban-García, P., Portillo, J., Ramírez, C., & Abián-Vicén, J. (2026). Beyond the FTO Gene: Environmental and Behavioural Factors Associated with BMI and Overweight in Spanish Adolescents. Children, 13(6), 782. https://doi.org/10.3390/children13060782 Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here. Article Metrics Article metric data becomes available approximately 24 hours after publication online.

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