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Original Article

Open Access Gateway

Association Study of Three Gene Polymorphisms Recently Identified by a Genome-Wide Association Study with Obesity-Related Phenotypes in Chinese Children

Song Q.-Y.a · Song J.-Y.b · Wang Y.b · Wang S.b · Yang Y.-D.b · Meng X.-R.b · Ma J.b · Wang H.-J.a, b · Wang Y.a

Author affiliations

aDepartment of Child, Adolescent and Women's Health, School of Public Health, Peking University, Beijing, China; bInstitute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China

Corresponding Author

Hai-Jun Wang

Institute of Child and Adolescent Health, Department of Child, Adolescent and Women's Health

School of Public Health, Peking University

No. 38 Xueyuan Road, Haidian District, 100191 Beijing, China

whjun1@bjmu.edu.cn

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Abstract

Objective: This study aimed to examine associations of three single-nucleotide polymorphisms (SNPs) with obesity-related phenotypes in Chinese children. These SNPs were identified by a recent genome-wide association (GWA) study among European children. Given that varied genetic backgrounds across different ethnicity may result in different association, it is necessary to study these associations in a different ethnic population. Methods: A total of 3,922 children, including 2,191 normal-weight, 873 overweight and 858 obese children, from three independent studies were included in the study. Logistic and linear regressions were performed, and meta-analyses were conducted to assess the associations between the SNPs and obesity-related phenotypes. Results: The pooled odds ratios of the A-allele of rs564343 in PACS1 for obesity and severe obesity were 1.180 (p = 0.03) and 1.312 (p = 0.004), respectively. We also found that rs564343 was nominally associated with BMI, BMI standard deviation score (BMI-SDS), waist circumference, and waist-to-height ratio (p < 0.05). Conclusions: We showed for the first time that the rs564343 in PACS1 was associated with risk of severe obesity in a non-European population. This SNP was also found to be associated with common obesity and various obesity-related phenotypes in Chinese children, which had not been reported in the original study. The results demonstrated the value of conducting genetic researches in populations with different ethnicity.

© 2017 The Author(s) Published by S. Karger GmbH, Freiburg


References

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  27. Ji CY: 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.
    External Resources
  28. Li H, Zong XN, Ji CY, Mi J: Body mass index cut-offs for overweight and obesity in Chinese children and adolescents aged 2-18 years. Zhonghua Liu Xing Bing Xue Za Zhi 2010;31:616-620.
    External Resources
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    External Resources
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  32. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents: The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555-576.
    External Resources
  33. Weir BS, Cockerham CC: Estimating F-statistics for the analysis of population structure. Evolution 1984;38:1358-1370.
  34. Duan S, Zhang W, Cox NJ, Dolan ME: FstSNP-HapMap3:a database of SNPs with high population differentiation for HapMap3. Bioinformation 2008;3:139-141.
  35. Balloux F, Lugon-Moulin N: The estimation of population differentiation with microsatellite markers. Mol Ecol 2002;11:155-165.
  36. Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. Br Med J 2003;327:557-560.
  37. Takkouche B, Cadarso-Suárez C, Spiegelman D: Evaluation of old and new tests of heterogeneity in epidemiologic meta-analysis. Am J Epidemiol 1999;150:206-215.
  38. Schuurs-Hoeijmakers JH, Oh EC, Vissers LE, Swinkels ME, Gilissen C, Willemsen MA, Holvoet M, Steehouwer M, Veltman JA, de Vries BB, van Bokhoven H, de Brouwer AP, Katsanis N, Devriendt K, Brunner HG: Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome. Am J Hum Genet 2012;91:1122-1127.
  39. Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G: PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization. Cell 1998;94:205-216.
  40. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN: Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 2003;33:177-182.

Article / Publication Details

First-Page Preview
Abstract of Original Article

Received: September 21, 2016
Accepted: March 09, 2017
Published online: June 01, 2017
Issue release date: June 2017

Number of Print Pages: 12
Number of Figures: 2
Number of Tables: 3

ISSN: 1662-4025 (Print)
eISSN: 1662-4033 (Online)

For additional information: https://www.karger.com/OFA

References

  1. Ng M, Fleming T, Robinson M, et al: Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013:a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384:766-781.
  2. Ogden CL, Carroll MD, Kit BK, Flegal KM: Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014;311:806-814.
  3. Ministry of Education of the People's Republic of China: Report on the physical fitness and health surveillance of Chinese school students (2010). Chi J School Health 2011;32:1024-1026.
  4. Haslam DW, James WPT: Obesity. Lancet 2005;366:1197-1209.
  5. Lean ME: Pathophysiology of obesity. The Proc Nutr Soc 2000;59:331-336.
    External Resources
  6. Mayer J: Genetic factors in human obesity. Ann Ny Acad Sci 1965;131:412-421.
  7. Li S, Zhao JH, Luan J, Luben RN, Rodwell SA, Khaw KT, Ong KK, Wareham NJ, Loos RJ: Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies. Am J Clin Nutr 2010;91:184-190.
  8. Chesi A, Grant SF: The genetics of pediatric obesity. Trends Endocrin Met 2015;26:711-721.
  9. Herbert A, Gerry NP, Mcqueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D, Hu FB: A common genetic variant is associated with adult and childhood obesity. Science 2006;312:279-283.
  10. Min J, Chiu DT, Wang Y: Variation in the heritability of body mass index based on diverse twin studies: a systematic review. Obes Rev 2013;14:871-882.
  11. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Lango AH, Lindgren CM, Luan J, Mägi R: Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010;42:937-948.
  12. Bradfield JP, Taal HR, Timpson NJ, et al: A genome-wide association meta-analysis identifies new childhood obesity loci. Nat Genet 2012;44:526-531.
  13. Berndt SI, Gustafsson S, Magi R, et al: Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nat Genet 2013;45:501-512.
  14. Locke AE, Bratati K, Berndt SI, Justice AE, Pers TH, Day FR, Corey P, Sailaja V, Buchkovich ML, Jian Y: Genetic studies of body mass index yield new insights for obesity biology. Nature 2015;518:197-206.
  15. Ioanna N, Kalliope P, Panagiota V, Lorraine S, Nigel WR, Eleftheria Z, Dedoussis GV: Replication of established common genetic variants for adult BMI and childhood obesity in Greek adolescents: the TEENAGE study. Ann Hum Genet 2013;77:268-274.
  16. Hong KW, Oh B: Recapitulation of genome-wide association studies on body mass index in the Korean population. Int J Obes 2012;36:1127-1130.
  17. Zhao J, Bradfield JP, Zhang H, Sleiman PM, Kim CE, Glessner JT, Deliard S, Thomas KA, Frackelton EC, Li M: Role of BMI-Associated Loci Identified in GWAS Meta-Analyses in the Context of Common Childhood Obesity in European Americans. Obesity (Silver Spring) 2011;19:2436-2439.
  18. Hong J, Shi J, Qi L, Cui B, Gu W, Zhang Y, Li L, Xu M, Wang L, Zhai Y: Genetic susceptibility, birth weight and obesity risk in young Chinese. Int J Obesity 2013;37:673-677.
  19. Wang HJ, Hinney A, Song JY, Scherag A, Meng XR, Grallert H, Illig T, Hebebrand J, Wang Y, Ma J: Association of common variants identified by recent genome-wide association studies with obesity in Chinese children: a case-control study. Bmc Med Genet 2016;17:7.
  20. Meng XR, Song JY, Ma J, Liu FH, Shang XR, Guo XJ, Wang HJ: Association study of childhood obesity with eight genetic variants recently identified by genome-wide association studies. Pediatr Res 2014;76:310-315.
  21. Wheeler E, Huang N, Bochukova EG, Keogh JM, Lindsay S, Garg S, Henning E, Blackburn H, Loos RJF, Wareham NJ, O'Rahilly S, Hurles ME, Barroso I, Farooqi IS: Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity. Nat Genet 2013;45:513-517.
  22. 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;21:528-536.
  23. Wang D, Ma J, Zhang S, Hinney A, Hebebrand J, Wang Y, Wang HJ: Association of the MC4R V103I polymorphism with obesity: a Chinese case-control study and meta-analysis in 55,195 individuals. Obesity (Silver Spring) 2010;18:573-579.
  24. Li BH, Wu SS, Li SS, Wang HJ, Ma J: Evaluation of school-based physical activity interventions for obesity in elementary students. Chin J School Health 2011;32:591-593.
  25. Pei ZC, Wang HJ, Li BH, Wang JJ, Ma J: Effects of health education of dietary nutrition on primary students in Beijing. Chin J School Health 2011;32:779-780.
  26. National Health and Family Planning Commission of PRC: WS/T 456-2014, Screening standard for malnutrition of school-age children and adolescents. China: NHFPC, 2014.
  27. Ji CY: 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.
    External Resources
  28. Li H, Zong XN, Ji CY, Mi J: Body mass index cut-offs for overweight and obesity in Chinese children and adolescents aged 2-18 years. Zhonghua Liu Xing Bing Xue Za Zhi 2010;31:616-620.
    External Resources
  29. Chinese Working Group on Obesity for Children: Report on the Physical Fitness and Health Surveillance of Chinese School Students (2005). Beijing, Higher Education Press, 2007, pp 220-222.
  30. World Health Organization: Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 1995;854:1-452.
    External Resources
  31. World Health Organization: Growth reference data for 5-19 years, www.who.int/growthref/en/ (last accessed May 16, 2017).
  32. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents: The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555-576.
    External Resources
  33. Weir BS, Cockerham CC: Estimating F-statistics for the analysis of population structure. Evolution 1984;38:1358-1370.
  34. Duan S, Zhang W, Cox NJ, Dolan ME: FstSNP-HapMap3:a database of SNPs with high population differentiation for HapMap3. Bioinformation 2008;3:139-141.
  35. Balloux F, Lugon-Moulin N: The estimation of population differentiation with microsatellite markers. Mol Ecol 2002;11:155-165.
  36. Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. Br Med J 2003;327:557-560.
  37. Takkouche B, Cadarso-Suárez C, Spiegelman D: Evaluation of old and new tests of heterogeneity in epidemiologic meta-analysis. Am J Epidemiol 1999;150:206-215.
  38. Schuurs-Hoeijmakers JH, Oh EC, Vissers LE, Swinkels ME, Gilissen C, Willemsen MA, Holvoet M, Steehouwer M, Veltman JA, de Vries BB, van Bokhoven H, de Brouwer AP, Katsanis N, Devriendt K, Brunner HG: Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome. Am J Hum Genet 2012;91:1122-1127.
  39. Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G: PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization. Cell 1998;94:205-216.
  40. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN: Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 2003;33:177-182.
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