Individual Genetic Variations Related to Satiety and Appetite Control Increase Risk of Obesity in Preschool-Age Children in the STRONG Kids Program

Abstract

Background/Aims: The burden of the childhood obesity epidemic is well recognized; nevertheless, the genetic markers and gene-environment interactions associated with the development of common obesity are still unknown. In this study, candidate genes associated to satiety and appetite control pathways with obesity-related traits were tested in Caucasian preschoolers from the STRONG Kids project. Methods: Eight genetic variants in genes related to obesity (BDNF, LEPR, FTO, PCSK1, POMC, TUB, LEP, and MC4R) were genotyped in 128 children from the STRONG Kids project (mean age 39.7 months). Data were analyzed for individual associations and to test for genetic predisposition scores (GPSs) with body mass index (BMI) and anthropometric traits (Z-scores, e.g. height-for-age Z-score, HAZ). Covariates included age, sex, and breastfeeding (BF) duration. Results: Obesity and overweight prevalence was 6.3 and 19.5%, respectively, according to age- and sex-specific BMI percentiles. Individual genetic associations of MC4R and LEPR markers with HAZ were strengthened when BF duration was included as a covariate. Our GPSs show that, as the number of risk alleles increased, the risk of higher BMI and HAZ also increased. Overall, the GPSs assembled were able to explain 2-3% of the variability in BMI and HAZ phenotypes. Conclusion: Genetic associations with common obesity-related phenotypes were found in the STRONG Kids project. GPSs assembled for specific candidate genes were associated with BMI and HAZ phenotypes.

Influence of genetic variants associated with body mass index on eating behavior in childhood

“…Although there is evidence in the literature for the role of MC4R , GNPDA2 , ADCY3/POMC , SCG3 , BBS4 , TUB , FTO , and SH2B1 in regulating appetite and/or satiety, we did not observe an association of SNPs in or near these genes with the eating behaviors . Again, this may be due to the relatively small sample size of our population.…”

“…In the previous GWAS paper, a manual literature search was performed into the potential roles of all genes within a region of 500 kb on either side (1 Mb total) of the 97 SNPs found to be associated with adult BMI . This showed that eight genes may play a role in appetite and satiety control . An additional literature search showed that FTO and BDNF may also play a role in appetite and satiety control, providing a total of 10 SNPs to test separately .…”

“…Some of these processes may influence eating behavior. Based on a literature review, 10 out of the 97 adult BMI SNPs, located in or near MC4R , GNPDA2 , ADCY3/POMC , LMX1B , SCG3 , BBS4 , TUB , FTO , BDNF , and SH2B1 , may also be associated with eating behavior through a potential role in the regulation of satiety and/or appetite .…”

The STRONG Kids 2 Birth Cohort Study: A Cell-to-Society Approach to Dietary Habits and Weight Trajectories across the First 5 Years of Life

“…Tubes were then placed into a storage box, which was placed into a sealable bag and stored in their home freezer (−20°C) until being picked up by the research staff. In addition, at the 6-wk visit, saliva samples were collected from both the mother and infant (18). However, in some cases insufficient amounts of saliva were obtained from the infant at 6 wk of age.…”

“…At the cellular level, variations in the maternal and child's genetic makeup as well as child and maternal microbiome are being examined using 16S ribosomal RNA sequencing and whole genome shotgun sequencing. Previous reports by our team have identified that candidate gene single nucleotide polymorphisms (SNPs) previously associated with an increased risk of overweight and obesity in adults (16, 17) also were associated with BMI in 2- to 3-y-olds (18). In the SK2 program, how route of delivery, maternal and child diet, maternal and child weight, and child growth trajectories affect the microbiome beginning at birth are being investigated.…”