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-naive (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-naive (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-naive 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.