Abstract

BackgroundLarge-scale genome-wide association studies have identified multiple genetic variants that are associated with elevated body mass index (BMI) or the risk of obesity in Caucasian or Asian populations. We examined whether these variants are individually associated with obesity in Chinese children, and also assessed their cumulative effects and predictive value for obesity risk in Chinese children.MethodsWe genotyped 40 single nucleotide polymorphisms (SNPs) and conducted association analyses for 32/40 SNPs with an estimated minor allele frequency >1 % in 2 030 unrelated Chinese children, including 607 normal-weight, 718 overweight, and 705 obese individuals from two cross-sectional study groups. Logistic regression and linear regression under the additive model were used to examine associations, and the area under the receiver operating characteristic curve (AUCROC) was reported as prediction summary.ResultsWe identified obesity association for 6 SNPs near SEC16B, RBJ, CDKAL1, TFAP2B, MAP2K5 and FTO (odds ratios (ORs) ranged from 1.19 to 1.41, nominal two-sided P-values < 0.05). Association (Bonferroni corrected) of rs543874 near SEC16B and rs2241423 near MAP2K5 had presumably stronger effects on obesity in Chinese children than in Caucasian populations. Their risk alleles were also associated with BMI standard deviation score (BMI-SDS) variability. We demonstrated the cumulative effects of the 32 SNPs on obesity risk (per risk allele: OR = 1.06, 95 % CI: 1.03-1.11, P = 4.84 × 10-4) and BMI-SDS (β = 0.04, 95 % CI: 0.02-0.06, P = 3.69 × 10-7). The difference in AUCROC for a model with covariates (age, age square, sex and study group) and the model including covariates and all 32 SNPs was 2.8 % (P = 0.0002).ConclusionWhile six SNPs were individually associated with obesity in Chinese children, the 32 common variants identified by recent GWA studies had cumulative effects and resulted in a limited increase in the AUCROC predictive value for childhood obesity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-016-0268-4) contains supplementary material, which is available to authorized users.

Highlights

  • Large-scale genome-wide association studies have identified multiple genetic variants that are associated with elevated body mass index (BMI) or the risk of obesity in Caucasian or Asian populations

  • Based on the FST values, we found that 23/28 single nucleotide polymorphism (SNPs) from three genome-wide association (GWA) studies of Europeans and 4/4 SNPs from two GWA studies of East Asians had similar effect allele frequencies in our study

  • We identified the nominally significant associations with obesity for effect alleles of 6 SNPs at FTO, SEC16B, TFAP2B, RBJ, MAP2K5 and CDKAL1 (ORs for the effect allele ranged between 1.19 and 1.41, nominal two-sided P < 0.05)

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Summary

Introduction

Large-scale genome-wide association studies have identified multiple genetic variants that are associated with elevated body mass index (BMI) or the risk of obesity in Caucasian or Asian populations. We examined whether these variants are individually associated with obesity in Chinese children, and assessed their cumulative effects and predictive value for obesity risk in Chinese children. In 2010, a meta-analysis of genome-wide association (GWA) studies for BMI was conducted in 249,796 adult individuals of European ancestry by the Genetic Investigation of Anthropometric Traits (GIANT) consortium They confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with BMI at a genomewide significance level (P < 5 × 10-8) [4]

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