The FTO rs9939609 Variant Is Associated with Cardiometabolic Disease Risk and Dietary Energy Intakes in Children with Mental Health Disorders

BACKGROUND: Second-generation antipsychotics (SGAs) are used to treat children for mental health disorders but in some children they cause cardiometabolic complications including weight gain and type 2 diabetes. Genetic variants can place a child at risk of developing these metabolic complications. The fat mass and obesity-associated (FTO) rs9939609 A allele has been associated with obesity and dietary energy intakes in healthy children but its relation to metabolic complications in SGA-treated children is not known. OBJECTIVES: This study investigated the association of the FTO rs9939609 variant and SGA treatment with cardiometabolic complications and dietary intakes in children with mental health disorders. METHODS: A cross-sectional population of children (≤18 y; n = 506) with mental health disorders that were SGA-treated (n = 197) and SGA-naïve (n = 309) were recruited through the Department of Psychiatry at BC Children's Hospital. Dietary intakes were estimated using 3-d food records in a subset of children (n = 73). RESULTS: Genotype frequencies were not different between SGA-treated (TT genotype 42.6%, TA genotype 38.6%, AA genotype 18.8%) and SGA-naïve (TT 41.1%, TA 39.5%, AA 19.4%) children. Children with the A allele had lower BMI z-sores compared with the TT genotype (0.84 ± 1.19 compared with 1.19 ± 1.36; P = 0.005, adjusted for ethnicity). We observed an interaction between FTO genotype and SGA status on fasting glucose (P = 0.036). SGA-naïve children with the A allele had higher fasting glucose than those with the TT genotype (4.96 ± 0.35 compared with 4.81 ± 0.35 mmol/L; P = 0.001), in adjusted models (age, sex, ethnicity, and BMI z-score). This was not observed in SGA-treated children. Children with the A allele had higher daily total energy intakes compared with the TT genotype (1994 ± 619 compared with 1814 ± 484 kcal/d; P = 0.048), in adjusted models (age, sex, ethnicity, and BMI z-score); no effect of SGA-treatment was observed. CONCLUSIONS: Our findings suggest the A allele of the FTO rs9939609 variant is associated with higher BMI in children with mental health disorders, but only in those not treated with SGAs.