Article | Published:

Pediatrics

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

International Journal of Obesity (2018) | Download Citation

Subjects

Abstract

Background/objectives

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 adult  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.

Subjects/methods

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).

Results

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.

Conclusions

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.

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Acknowledgements

We thank all the study participants and the reviewers for their helpful comments. We thank Carolina Stryjecki for her technical assistance. D.M. is supported by a Tier 2 Canada Research Chair in Genetics of Obesity. This work was supported by Fundación IMSS A.C. and by the National Council of Science and Technology (CONACYT-México) with the grant SALUD-2013-C01-201471 (FONSEC SSA/IMSS/ISSSTE).

Author information

Affiliations

  1. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada

    • Michelle Turcotte
    • , Arkan Abadi
    • , Hudson Reddon
    •  & David Meyre
  2. Medical Research Unit in Biochemistry, Hospital de Especialidades, Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social, Mexico City, Mexico

    • Jesus Peralta-Romero
    • , Fernando Suarez
    • , Jaime Gomez-Zamudio
    •  & Miguel Cruz
  3. Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico

    • Ana I. Burguete-Garcia
  4. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada

    • David Meyre

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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding authors

Correspondence to Miguel Cruz or David Meyre.

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DOI

https://doi.org/10.1038/s41366-018-0055-8