Genetic determinants of BMI from early childhood to adolescence: the Santiago Longitudinal Study

Abstract

Summary Background While the genetic contribution to obesity is well established, few studies have examined how genetic variants influence standardized body mass index Z‐score (BMIz) in Hispanics/Latinos, especially across childhood and adolescence. Objectives We estimated the effect of established BMIz loci in Chilean children of the Santiago Longitudinal Study (SLS). Methods We examined associations with BMIz at age 10 for 15 loci previously identified in European children. For significant loci, we performed association analyses at ages 5 and 16 years, for which we have smaller sample sizes. We tested associations of unweighted genetic risk scores (GRSs) for previously identified tag variants (GRS_EUR) and from the most significant variants in SLS at each locus (GRS_SLS). Results We generalized five variants at age 10 (P < 0.05 and directionally consistent), including rs543874 that reached Bonferroni‐corrected significance. The effect on BMIz was greatest at age 10 for all significant loci, except FTO, which exhibited an increase in effect from ages 5 to 16. Both GRSs were associated with BMIz (P < 0.0001), but GRS_SLS explained a much greater proportion of the variation (13.63%). Conclusion Our results underscore the importance of conducting genetic investigations across life stages and selecting ancestry appropriate tag variants in future studies for disease prediction and clinical evaluation.

Exclusive breastfeeding can attenuate body-mass-index increase among genetically susceptible children: A longitudinal study from the ALSPAC cohort

“…The role of the obesity-specific GRS has been recently studied in children and adolescents [10][11][12][13][23][24][25][26][27][28] and recent evidence suggests a continuum of risks starting from early childhood [12] and rising up to the mid 40s [10]. Our study confirms this trend and helps better characterize the GRS effect during childhood, showing a clear increasing trend from early infancy to late adolescence/early adulthood in boys and girls.…”

Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose–Lipid Metabolism

“…Our research included older children (6.6–17.7, median 14.6), which may suggest that the impact of the FTO gene on the risk of obesity increases with age. This supposition was confirmed by a study conducted on a group of children from 5 to 16 years old, showing a positive influence of the rs1421085 FTO gene polymorphism on the BMI as the age of the subjects increased [ 7 ]. The fact that it was mainly the variability of region 1 of the FTO gene that affected body weight was confirmed by other studies [ 5 , 46 , 47 , 48 ].…”

“…Although the impact of environmental factors, like a sedentary lifestyle and excessive nutrient supply, has a large contribution to the end result, more attention should be paid to other relevant obesity-related factors [ 4 ]. Many studies, also in the pediatric population, focus on single nucleotide polymorphisms (SNPs) in genes with a well-described relationship with obesity, such as FTO [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], or genes, whose role in obesity is recently gradually being discovered, as the PLAG1 gene [ 16 , 17 , 18 ]. However, very few studies address the impact of epigenetics, including the DNA methylation of CpG dinucleotides, on this phenomenon [ 19 , 20 ].…”

Asociación entre el polimorfismo rs9939609 del gen FTO y marcadores de adiposidad en población infantil chilena

“…Esta observación es consistente con un estudio reciente, donde se encontró que la asociación de IMC con diversos loci de predisposición genética a obesidad cambia a lo largo del curso del desarrollo en los niños del Estudio Longitudinal de Santiago. Particularmente, se observó que la mayor asociación entre IMC-z score y la mayoría de los loci se producen a los 10 años de edad, a excepción de FTO, el que puede alcanzar su máximo efecto hasta los 16 años 27 .…”