Running title: BDNF AA genotype from Val66Met SNP associates with pediatric overweight and obesity Mexico has one of the highest pediatric overweight and obesity prevalence BDNF has been associated with body weight regulation. The BDNF rs6265 SNP (G196A; Val66Met) has been associated with eating disorders, BMI and obesity, with contradictory results in both adults and children. We found significant associations between BDNF Val66Met AA (Met/) genotype and overweight/obesity in Mexican pediatric population Met homozygote children/adolescents increased the risk almost seven times of being classified in the overweight group (Ow+Ob) relative to Val carriers Abbreviations BDNF, brain-derived neurotrophic Abstract Background: The functional brain-derived neurotrophic factor (BDNF) rs6265 (G196A; Val66Met) single nucleotide polymorphism has been associated with eating disorders, BMI and obesity in distinct populations, both adult and pediatric, with contradictory results involving either Val or Met as the risk variant. Aim of the study: To determine the association between the BDNF Val66Met polymorphism and BMI in Mexican children and adolescents. Methods: BDNF Val66Met genotyping by restriction fragment length polymorphism and nutritional status characterized by their BMI-for-age z-scores (BAZ) from pediatric volunteers recruited in Mexico City (n=498) were analyzed by Fisher's exact test association analysis. Standardized residuals (R) were used to determine which genotype/allele had the major influence on the significant Fisher's exact test statistic. Odds ratios were analyzed to measure the magnitude and direction of the association between genotype and normal weight (≥ -2 SD < +1 SD) and overweight (≥ +1 SD, including obesity, Ow+Ob) status with 95% confidence intervals to estimate the precision of the effect as well as 95% credible intervals to obtain the most probable estimate. Results: Comparisons between GG (Val/Val), GA (Val/Met) and AA (Met/Met) genotypes or Met homozygotes vs. Val carriers (combination of GG and GA genotypes) showed significant differences (p=0.034 and p=0.037, respectively) between normal weight and the combined overweight and obese pediatric subjects. Our data showed that children/adolescents homozygous for the A allele have increased risk of overweight compared to the Val carriers (Bayes OR= 4.2, 95% CI**[1.09 -33.1]). Conclusion: This is the first study showing the significant association between the BDNF rs6265 AA (Met/Met) genotype and overweight/obesity in Mexican pediatric population. 4