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

Abstract

Background Second-generation antipsychotics (SGAs) are used to treat children for mental health disorders but in some children cause cardiometabolic complications including weight gain and type 2 diabetes. Genetic variants may place a child at risk for 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 relationship to metabolic complications in SGA-treated children is not known. Objective 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. Design A cross-sectional population of children (≤18y;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 three-day food records in a subset of children (n = 73). Results Genotype frequencies were not different between SGA-treated (TT 42.6%, TA 38.6%, AA 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 to the TT genotype (0.84±1.19 vs 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 vs 4.81±0.35 mmol/L;P = 0.001), in adjusted models (age, sex, ethnicity, and zBMI). This was not observed in SGA-treated children. Children with the A allele had higher daily total energy intakes compared to the TT genotype (1994±619 vs. 1814±484 kcal/d;P = 0.048), in adjusted models (age, sex, ethnicity, and zBMI; no effect of SGA-treatment was observed. Conclusion 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.

Polymorphisms of Fat Mass and Obesity-Associated Gene in the Pathogenesis of Child and Adolescent Metabolic Syndrome

“…These results indicate that the A allele carriers consumed more food due to their better appetite. In several other populations of children and adolescents from Europe and Canada [ 107 , 108 , 109 ], researchers also demonstrated a significant association of the rs9939609 and rs1421085 polymorphisms with total energy intake. Increased energy intake in children and adolescents with specific FTO genotypes may be due to their preference for high-energy foods such as those containing fat.…”