Abstract
Background:
Being overweight or obese is becoming increasingly common in low- and middle-income countries. The present study aimed to examine association of eight genetic variants with obesity and to estimate the cumulative effects of these variants in Chinese children.
Methods:
We conducted the case–control study in a total of 2,030 subjects. Genotyping of seven novel variants was performed with matrix-assisted laser desorption ionization time of flight mass spectrometry, while rs9939609 was genotyped with tetra-primer amplification refractory mutation system analysis.
Results:
The association of two fat mass and obesity-associated gene (FTO) single-nucleotide polymorphisms (SNPs; rs9939609 and rs62048402) with body mass index (BMI) or obesity reached nominal significance at P < 0.05. We found a cumulative effect of five SNPs on the risk of overweight and obesity (odds ratio (OR) = 1.197, 95% confidence interval (CI) = 1.068–1.342, P = 0.002). Subjects carrying 9 or more effect alleles had a 127% increased risk of overweight and obesity (OR = 2.270, 95% CI = 1.403–3.671, P = 0.001) compared with subjects who carry 6 or fewer effect alleles.
Conclusion:
We confirmed two FTO SNPs (rs62048402 and rs9939609) had nominal significant effects on BMI or obesity. We identified the cumulative effect of five SNPs on risk of overweight and obesity. The results provided evidence for identifying genetic factors related to childhood obesity.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Lombard Z, Crowther NJ, van der Merwe L, Pitamber P, Norris SA, Ramsay M . Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study. BMJ Open 2012;2:e000873.
Herbert A, Gerry NP, McQueen MB, et al. A common genetic variant is associated with adult and childhood obesity. Science 2006;312:279–83.
Speliotes EK, Willer CJ, Berndt SI, et al.; MAGIC; Procardis Consortium. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010;42:937–48.
Qi Q, Chu AY, Kang JH, et al. Sugar-sweetened beverages and genetic risk of obesity. N Engl J Med 2012;367:1387–96.
Ntalla I, Panoutsopoulou K, Vlachou P, et al. Replication of established common genetic variants for adult BMI and childhood obesity in Greek adolescents: the TEENAGE study. Ann Hum Genet 2013;77:268–74.
Monda KL, Chen GK, Taylor KC, et al.; NABEC Consortium; UKBEC Consortium; BioBank Japan Project; AGEN Consortium. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet 2013;45:690–6.
Ng MC, Hester JM, Wing MR, et al. Genome-wide association of BMI in African Americans. Obesity (Silver Spring) 2012;20:622–7.
Wang KS, Liu X, Zheng S, Zeng M, Pan Y, Callahan K . A novel locus for body mass index on 5p15.2: a meta-analysis of two genome-wide association studies. Gene 2012;500:80–4.
Sällman Almén M, Rask-Andersen M, Jacobsson JA, et al. Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children. Int J Obes (Lond) 2013;37:424–31.
Xi B, Cheng H, Shen Y, et al. Study of 11 BMI-associated loci identified in GWAS for associations with central obesity in the Chinese children. PLoS ONE 2013;8:e56472.
da Silva CF, Zandoná MR, Vitolo MR, et al. Association between a frequent variant of the FTO gene and anthropometric phenotypes in Brazilian children. BMC Med Genet 2013;14:34.
Fava C, Sjögren M, Montagnana M, et al. Prediction of blood pressure changes over time and incidence of hypertension by a genetic risk score in Swedes. Hypertension 2013;61:319–26.
Li S, Zhao JH, Luan J, et al. Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies. Am J Clin Nutr 2010;91:184–90.
Berthoud HR, Morrison C . The brain, appetite, and obesity. Annu Rev Psychol 2008;59:55–92.
Willer CJ, Speliotes EK, Loos RJ, et al.; Wellcome Trust Case Control Consortium; Genetic Investigation of ANthropometric Traits Consortium. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009;41:25–34.
Razquin C, Marti A, Martinez JA . Evidences on three relevant obesogenes: MC4R, FTO and PPAR? Approaches for personalized nutrition. Mol Nutr Food Res 2011;55:136–49.
Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN . An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 2008;359:2558–66.
Balloux F, Lugon-Moulin N . The estimation of population differentiation with microsatellite markers. Mol Ecol 2002;11:155–65.
Bradfield JP, Taal HR, Timpson NJ, et al.; Early Growth Genetics Consortium. A genome-wide association meta-analysis identifies new childhood obesity loci. Nat Genet 2012;44:526–31.
Scherag A, Dina C, Hinney A, et al. Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups. PLoS Genet 2010;6:e1000916.
Hai-Jun W, Jun M, Zun-Dong Y, Yi-Qun X, Yong-Ping P . Study on the relationship between obesity and metabolic syndrome in adolescents. Chin J Sch Health 2007;28:878–82.
Jun M, Shi-Wei Z, Sheng-Xin W, Heng Z, Shan-Shan L . Prevalence of metabolic syndrome among children with different nutritional status in Beijing. Chin J Sch Health 2008;29:103–5.
Wang D, Ma J, Zhang S, et al. Association of the MC4R V103I polymorphism with obesity: a Chinese case-control study and meta-analysis in 55,195 individuals. Obesity (Silver Spring) 2010;18:573–9.
Wang HJ, Zhang H, Zhang SW, Pan YP, Ma J . Association of the common genetic variant upstream of INSIG2 gene with obesity related phenotypes in Chinese children and adolescents. Biomed Environ Sci 2008;21:528–36.
Ji CY ; Working Group on Obesity in China. Report on childhood obesity in China (1)–body mass index reference for screening overweight and obesity in Chinese school-age children. Biomed Environ Sci 2005;18:390–400.
Ye S, Dhillon S, Ke X, Collins AR, Day IN . An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res 2001;29:E88–8.
Weir BS, Cockerham CC . Estimating F-statistics for the analysis of population structure. Evolution 1984;38:1358–1370.
Duan S, Zhang W, Cox NJ, Dolan ME . FstSNP-HapMap3: a database of SNPs with high population differentiation for HapMap3. Bioinformation 2008;3:139–41.
Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263–5.
Che R, Motsinger-Reif AA . Evaluation of genetic risk score models in the presence of interaction and linkage disequilibrium. Front Genet 2013;4:138.
Author information
Authors and Affiliations
Corresponding author
PowerPoint slides
Rights and permissions
About this article
Cite this article
Meng, XR., Song, JY., Ma, J. et al. Association study of childhood obesity with eight genetic variants recently identified by genome-wide association studies. Pediatr Res 76, 310–315 (2014). https://doi.org/10.1038/pr.2014.88
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2014.88
This article is cited by
-
The association between living environmental factors and adolescents’ body weight: a cross-sectional study
BMC Pediatrics (2021)
-
Genetic variants in the FAM3C gene are associated with lipid traits in Chinese children
Pediatric Research (2021)
-
Interaction between lifestyle behaviors and genetic polymorphism in SCAP gene on blood pressure among Chinese children
Pediatric Research (2019)
-
Waist-hip ratio related genetic loci are associated with risk of impaired fasting glucose in Chinese children: a case control study
Nutrition & Metabolism (2018)
