Abstract
OBJECTIVE: The importance of the central and peripheral serotonin systems in regulating energy balance and obesity development has been highlighted in animal models. Yet, the role of both serotonin systems has not been systematically assessed in humans. The purpose of this study was to investigate the association of genes within both serotonin systems with obesity outcomes in black adolescents. METHODS: African-American adolescents (n = 1052) whose mothers participated the Memphis New Mother's Study were assessed. In total, 110 polymorphisms mapped to 10 serotonin genes were examined for their associations with standardized body mass index (BMI-z) scores and waist circumferences using generalized estimating equation models. RESULTS: Over 39% of adolescents were overweight or had obesity. Three single nucleotide polymorphisms (SNPs) within TPH2, HTR3B, and SLC6A4, were significantly associated with BMI-z scores (p < 1.7 × 10(-3)). Two SNPs in TPH2 were nominally associated with waist circumferences. One SNP in HTR2C was associated with BMI-z scores (p = 0.001) and waist circumferences (p = 0.005) only in girls. Tissue-specific expression indicates that three identified genes are predominantly expressed in the brain. CONCLUSION: The central serotonin system may play a key role in obesity development in black adolescents. Future studies are warranted to explore additional serotonin system genes and their potential obesogenic mechanisms in humans.