title: Association of common variants identified by recent genome-wide association studies with obesity in Chinese children: a case-control study.
abstract: BACKGROUND
  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 also assessed their cumulative effects and predictive value for obesity risk in Chinese children.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  We 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).
  
  
  CONCLUSIONS
  While 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.
authors.affiliation: Institute of Child and Adolescent Health, Peking University, Beijing, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
authors.affiliation: Institute of Child and Adolescent Health, Peking University, Beijing, China.
authors.forename: Jie-Yun
authors.initials: JY
authors.lastname: Song
authors.affiliation: Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, 07743, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.affiliation: Institute of Child and Adolescent Health, Peking University, Beijing, China.
authors.forename: Xiang-Rui
authors.initials: XR
authors.lastname: Meng
authors.affiliation: Research Unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.affiliation: Research Unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.affiliation: Division of Maternal and Child Health, School of Public Health, Peking University Health Science Center, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Child and Adolescent Health, Peking University, Beijing, China. majunt@bjmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002681:China; D003430:Cross-Sectional Studies; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D050956:HSP40 Heat-Shock Proteins; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D048671:MAP Kinase Kinase 5 / Q000235:genetics; D008297:Male; D050177:Overweight / Q000235:genetics; D063766:Pediatric Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000235:genetics; D044465:White People / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics; D012359:tRNA Methyltransferases
chemical_list: D004268:DNA-Binding Proteins; D050956:HSP40 Heat-Shock Proteins; D011506:Proteins; C443860:SEC16B protein, human; C493677:TFAP2B protein, human; D050656:Transcription Factor AP-2; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human; C525110:CDKAL1 protein, human; C000589559:DNAJC27 protein, human; D020691:rab GTP-Binding Proteins