title: Obesity-susceptibility loci and the tails of the pediatric BMI distribution.
abstract: OBJECTIVE
  To determine whether previously identified adult obesity susceptibility loci were associated uniformly with childhood BMI across the BMI distribution.
  
  
  METHODS
  Children were recruited through the Children's Hospital of Philadelphia (n = 7,225). Associations between the following loci and BMI were assessed using quantile regression: FTO (rs3751812), MC4R (rs12970134), TMEM18 (rs2867125), BDNF (rs6265), TNNI3K (rs1514175), NRXN3 (rs10146997), SEC16B (rs10913469), and GNPDA2 (rs13130484). BMI z-score (age and gender adjusted) was modeled as the dependent variable, and genotype risk score (sum of risk alleles carried at the 8 loci) was modeled as the independent variable.
  
  
  RESULTS
  Each additional increase in genotype risk score was associated with an increase in BMI z-score at the 5th, 15th, 25th, 50th, 75th, 85th, and 95th BMI z-score percentiles by 0.04 (±0.02, P = 0.08), 0.07 (±0.01, P = 9.58 × 10(-7) ), 0.07 (±0.01, P = 1.10 × 10(-8) ), 0.09 (±0.01, P = 3.13 × 10(-22) ), 0.11 (±0.01, P = 1.35 × 10(-25) ), 0.11 (±0.01, P = 1.98 × 10(-20) ), and 0.06 (±0.01, P = 2.44 × 10(-6) ), respectively. Each additional increase in genotype risk score was associated with an increase in mean BMI z-score by 0.08 (±0.01, P = 4.27 × 10(-20) ).
  
  
  CONCLUSIONS
  Obesity risk alleles were more strongly associated with increases in BMI z-score at the upper tail compared to the lower tail of the distribution.
authors: Center for Genetics and Complex Traits, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, USA. jmitch@mail.med.upenn.edu
authors: Jonathan A
authors: JA
authors: Mitchell
authors: Hakon
authors: H
authors: Hakonarson
authors: Timothy R
authors: TR
authors: Rebbeck
authors: Struan F A
authors: SF
authors: Grant
mesh_terms: D000293:Adolescent; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics*; D015143:Philadelphia; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C443860:SEC16B protein, human; C082354:neurexin IIIalpha; C579455:BDNF protein, human; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human