Validation of obesity susceptibility loci identified by genome-wide association studies in early childhood in South Brazilian children.

BACKGROUND:The prevalence of childhood obesity has been dramatically increasing in developing countries as it has been reported for developed nations. Identifying susceptibility genes in early life could provide the foundations for interventions in lifestyle to prevent obese children to become obese adults. OBJECTIVES:The objective of this study was to evaluate the influence of genetic variants related to obesity identified by genome-wide association studies (MC4R, TMEM18, KCTD15, SH2B1, SEC16B, BDNF, NEGR1, OLFM4 and HOXB5 genes) on anthropometric and dietary phenotypes in two Brazilian cohorts followed-up since birth. METHODS:There were 745 children examined at birth, after 1 year and after 3.5 years of follow-up. Ten single nucleotide polymorphisms were genotyped. Anthropometric and dietary parameters were compared among genotypes. Children were classified as overweight when body mass index Z-score was >+1. RESULTS:Overweight prevalence was 30.7% at 3.5 years old. Significant associations were identified at 3.5 years old for TMEM18 rs6548238, NEGR1 rs2815752, BDNF rs10767664 and rs6265 (1 year old and 3.5 years old) with anthropometric phenotypes and at 3.5 years old for SEC16B rs10913469 with dietary parameters. CONCLUSIONS:Our results indicate that genetic variants in/near these genes contribute to obesity susceptibility in childhood and highlight the age at which they begin to affect obesity-related phenotypes.

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