Genetic contribution to waist-to-hip ratio in Mexican children and adolescents based on 12 loci validated in European adults.
Int J Obes (Lond)
; 43(1): 13-22, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-29777226
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 (ß = 0.733 ± 0.190, P = 1.1 × 10-4) and LDL-C (ß = 0.491 ± 0.203, P = 1.6 × 10-2), and negatively associated with HDL-C (ß = -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 (ß = 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 (ß = 0.022 ± 0.012, P = 4.7 × 10-2) and the GS (ß = 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo de Nucleótido Simple
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Relación Cintura-Cadera
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Estudio de Asociación del Genoma Completo
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Obesidad Abdominal
Tipo de estudio:
Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
País como asunto:
Europa
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Mexico
Idioma:
En
Año:
2019
Tipo del documento:
Article