Common Variants of FTO Are Associated with Childhood Obesity in a Cross-Sectional Study of 3,126 Urban Indian Children

Background: FTO variants are robustly associated with obesity and related traits in many population and shown to have variable impact during life course. Although studies have shown association of FTO variants with adiposity in adult Indian, its association in Indian children is yet to be confirmed. Methods: Here we examined association of FTO variants (rs9939609 and rs8050136) with obesity and related anthropometric and biochemical traits in 3,126 Indian children (aged 11-17 years) including 2,230 normal-weight and 896 over-weight/obese children. We also compared effects observed in the present study with that observed in previous studies on South Asian adults and children of other ethnic groups. Results: The variant rs9939609 showed significant association with risk of obesity [OR = 1.21, P = 2.5x10(-3)] and its measures BMI, weight, waist circumference and hip circumference [beta range = 0.11 to 0.14 Z-score units; P range = 1.3x10(-4) to 1.6x10(-7)] in children. The observed effect sizes in Indian children were similar to those reported for European children. Variant rs9939609 explained 0.88% of BMI variance in Indian children. The effect sizes of rs9939609 on BMI and WC were similar to 2 fold higher in children than adults. Interestingly rs9939609 was also associated with serum levels of thyroid stimulating hormone (TSH) [beta = 0.10 Z-score, P = 5.8x10(-3)]. The other variant rs8050136 was in strong linkage disequilibrium with rs9939609 (r(2) = 0.97) and provided similar association results. Conclusion: The study provides first report of association of FTO variants with obesity and related anthropometric traits in Indian children with higher impact in children compared to adults. We also demonstrated association of FTO variant with serum levels of TSH, indicating putative influence of FTO in hypothalamic-pituitary-thyroid axis.