Childhood obesity is a global health concern due to its potential to increase cardiometabolic risk across the life course. In the United States (US) the burden of childhood obesity is highest among Hispanic/Latinos, in particular children or adolescents of Mexican descent. Although the genetic epidemiology of childhood obesity has been studied previously, the potential for novel childhood obesity loci in Hispanic/Latinos and the generalizability of previously reported loci to Hispanic/Latino children and adolescents are still unknown. Thus we aimed to conduct a genome-wide association study of childhood obesity in 1,612 Hispanic/Latino children and adolescents (2-18 years) collected as part of one Mexican (n=794 Mexico City Study) and two US (n=362 Children’s Hospital of Philadelphia; n=456 Viva La Familia Study) studies, and to generalize 11 previously reported childhood obesity loci from European descent samples to our Hispanic/Latino samples. Obesity cases and controls were defined by BMI-for-age percentiles based on the Centers for Disease Control and Prevention smoothed and sex-specific growth curves from 2000, wherein cases had percentiles ≥95
th
and controls had percentiles ≤85
th
. Each study performed a genome-wide logistic regression analysis of single nucleotide polymorphism (SNPs) after adjusting for sex, population stratification and relatedness, as applicable. We combined study results for SNPs >10 minor allele counts and imputation quality ≥0.5 using fixed-effect inverse-variance weighted meta-analysis.
A priori,
we estimated that in our sample (n
effective
=1,498) we would have >80% power to detect common SNPs (>15% minor allele frequency) across the genome (p<5x10
-8
) that increase the odds of childhood obesity of 55% per risk allele. Generalizability at 11 known childhood obesity loci was defined as p<0.05 and directional consistency with the previously reported obesity-increasing allele. We found 5 suggestive childhood obesity loci (p<4x10
-6
), including a SNP that associated with an increased odds of childhood obesity of 54% per risk allele (73% frequent) at
ARHGAP21,
which is expressed in an enhancer region in brain, muscle and adipose tissues and has been previously implicated with trunk fat mass in Viva la Familia at another SNP (r
2
<0.08). Of the 11 known childhood obesity loci, 9 were directionally consistent (binomial p=0.03).
SEC16B
and
TMEM18
generalized to Hispanic/Latinos (p≤0.01), corresponding to a 27% and 40% increased odds of obesity per risk allele (22-88% frequency). These preliminary results suggest the presence of novel loci for childhood obesity and the generalizability of genetic loci discovered in samples of European descent to Hispanic/Latinos, albeit with stronger effect sizes. Future work will attempt to identify additional Hispanic/Latino obesity cases and controls to replicate the suggestive associations.
Trends of Child's Weight Perception by Children, Parents, and Healthcare Professionals during the Time of Terminology Change in Childhood Obesity in the United States, 2005–2014
