Laboratorio de Medicina Genómica, Hospital Regional Lic. Adolfo López Mateos, ISSSTE. 1321 Universidad Avenue, Álvaro Obregón, Florida, Mexico City P.C0103, Mexico.
Departamento de Métodos Cuantitativos, Facultad de Medicina, Universidad de la República, 2125 General Flores Avenue, Montevideo P.C11800, Uruguay.
Genes (Basel). 2019 Nov 19;10(11):945. doi: 10.3390/genes10110945.
Childhood obesity is a major health problem in Mexico. Obesity prevalence estimated by body mass index (BMI) is almost half than that estimated by percent body fat (%BF) in the Childhood Obesity pediatric cohort (COIPIS).
We performed a genome-wide association study (GWAS) of BMI and %BF in 828 children from the COIPIS to identify markers of predisposition to high values for both phenotypes used for obesity classification.
For the GWAS we used the LAT Axiom 1, Affymetrix and 2.5 million single loci from the 1000 Genomes Phase 3 imputation panel. We used a linear model, adjusted by age, sex, and Amerindian ancestry assuming an additive inheritance model.
Genome-wide significance (p ≤ 5.0 × 10) and 80% of statistical power was reached for associations of two loci in two genes (CERS3 and CYP2E1) to BMI. Also, 11 loci in six genes (ANKS1B, ARNTL2, KCNS3, LMNB1, SRGAP3, TRPC7) reached genome-wide significance for associations to %BF, though not 80% of statistical power.
None of the SNPs were previously reported as being associated to BMI or %BF. In addition, different loci were found for BMI and %BF. These results highlight the importance of gaining deeper understanding of genetic markers of predisposition to high values for the phenotypes used for obesity diagnosis.
儿童肥胖是墨西哥的一个主要健康问题。根据身体质量指数(BMI)估计的肥胖患病率几乎是儿童肥胖儿科队列(COIPIS)中根据体脂肪百分比(%BF)估计的肥胖患病率的一半。
我们对来自 COIPIS 的 828 名儿童进行了 BMI 和 %BF 的全基因组关联研究(GWAS),以鉴定两种表型(用于肥胖分类的 BMI 和 %BF)高值易感性的标记物。
对于 GWAS,我们使用了 LAT Axiom 1、Affymetrix 和来自 1000 基因组计划第三阶段的 250 万个单核苷酸多态性(SNP)进行了 GWAS。我们使用线性模型,通过年龄、性别和美洲印第安人祖先进行调整,假设加性遗传模型。
两个基因(CERS3 和 CYP2E1)的两个位点与 BMI 的关联达到了全基因组显著水平(p ≤ 5.0 × 10)和 80%的统计效力。此外,六个基因(ANKS1B、ARNTL2、KCNS3、LMNB1、SRGAP3、TRPC7)的 11 个位点与 %BF 的关联达到了全基因组显著水平,但未达到 80%的统计效力。
没有一个 SNP 之前被报道与 BMI 或 %BF 有关。此外,还发现了不同的与 BMI 和 %BF 相关的基因座。这些结果强调了深入了解用于肥胖诊断的表型的高值易感性遗传标记的重要性。