Michelle Turcotte1, Arkan Abadi1, Jesus Peralta-Romero2, Fernando Suarez2, Hudson Reddon1, Jaime Gomez-Zamudio2, Ana I Burguete-Garcia3, Miguel Cruz4, David Meyre5,6. 1. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada. 2. Medical Research Unit in Biochemistry, Hospital de Especialidades, Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social, Mexico City, Mexico. 3. Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico. 4. Medical Research Unit in Biochemistry, Hospital de Especialidades, Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social, Mexico City, Mexico. mcruzl@yahoo.com. 5. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada. meyred@mcmaster.ca. 6. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada. meyred@mcmaster.ca.
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.
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). HOXC13rs1443512 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 HOXC13rs1443512 and the GS on WHR (P = 2.2 × 10-2 and 1.2 × 10-2, respectively). HOXC13rs1443512 (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.
Authors: Erika Chavira-Suárez; Angélica Jazmín Ramírez-Mendieta; Sofía Martínez-Gutiérrez; Paola Zárate-Segura; Jorge Beltrán-Montoya; Nidia Carolina Espinosa-Maldonado; Juan Carlos de la Cerda-Ángeles; Felipe Vadillo-Ortega Journal: PLoS One Date: 2019-12-03 Impact factor: 3.240