Genetic contribution to waist-to-hip ratio in Mexican children and adolescents based on 12 loci validated in European adults

The prevalence of abdominal obesity in Mexican children has risen dramatically in the past decade. Genome-wide association studies (GWAS) for waist-to-hip ratio (WHR) performed predominantly in European descent populations have identified multiple single-nucleotide polymorphisms (SNPs) with larger effects in women. The contribution of these SNPs to WHR in non-European children is unknown. Mexican children and adolescents (N = 1421, 5–17 years) were recruited in Mexico City. Twelve GWAS SNPs were genotyped using TaqMan Open Array and analyzed individually and as a gene score (GS). Mexican boys and girls displayed 2.81 ± 0.29 and 3.10 ± 0.31 WHR standard deviations higher than children and adolescents from the United States. WHR was positively associated with TG (β = 0.733 ± 0.190, P = 1.1 × 10−4) and LDL-C (β = 0.491 ± 0.203, P = 1.6 × 10−2), and negatively associated with HDL-C (β = −0.652 ± 0.195, P = 8.0 × 10−4), independently of body mass index. The effect allele frequency (EAF) of 8 of 12 (67%) SNPs differed significantly (P < 4.17 × 10−3) in Mexican children and European adults, with no evidence of effect allele enrichment in both populations (4 depleted and 4 enriched; binomial test, P = 1). Ten out of 12 SNPs (83.3%) had effects that were directionally consistent with those reported in GWAS (P = 0.04). HOXC13 rs1443512 displayed the best fit when modeled recessively, and was significantly associated with WHR under a recessive mode of inheritance (β = 0.140 ± 0.06, P = 2.3 × 10−2). Significant interactions with sex were also observed for HOXC13 rs1443512 and the GS on WHR (P = 2.2 × 10−2 and 1.2 × 10−2, respectively). HOXC13 rs1443512 (β = 0.022 ± 0.012, P = 4.7 × 10−2) and the GS (β = 0.007 ± 0.003, P = 7.0 × 10−3) were significantly associated with WHR in girls only. This study demonstrates that Mexican children are at high risk for abdominal obesity and detrimental lipid profiles. Our data support a partial transferability of sex-specific European GWAS WHR association signals in children and adolescents from the admixed Mexican population.