Abstract P140: The Association of Common Genetic Loci with Childhood Obesity in 1,612 Hispanic/Latino Children and Adolescents From Across the United States and Mexico
Authors: Lindsay Fernández-Rhodes, Mariaelisa Graff, Jonathan Bradfield, Yujie Wang, Esteban J Parra, Miguel Cruz, Jesús Peralta-Romero, Astride Audirac-Chalifour, Bertha Hidalgo, Heather Highland, Anthony G Comuzzie, Nancy F Butte, Shelley A Cole, V. S Voruganti, Christopher Haiman, Ruth F Loos, Kari E North
Journal: Circulation (2017)

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 &gt;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 &gt;80% power to detect common SNPs (&gt;15% minor allele frequency) across the genome (p&lt;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&lt;0.05 and directional consistency with the previously reported obesity-increasing allele. We found 5 suggestive childhood obesity loci (p&lt;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 &lt;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.