Genetic Determinants of BMI From Early Childhood to Adolescence: The Santiago Longitudinal Study

Pediatr Obes. 2019 Mar;14(3):e12479. doi: 10.1111/ijpo.12479. Epub 2018 Dec 4.

Abstract

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.

Keywords: BMI; Latin America; genetic risk score; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Body Mass Index*
  • Child
  • Child Development / physiology
  • Child, Preschool
  • Chile
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Pediatric Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Risk Factors