Premium
Obesity‐susceptibility loci and the tails of the pediatric BMI distribution
Author(s) -
Mitchell Jonathan A.,
Hakonarson Hakon,
Rebbeck Timothy R.,
Grant Struan F.A.
Publication year - 2013
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20319
Subject(s) - percentile , medicine , obesity , body mass index , genotype , childhood obesity , demography , allele , overweight , genetics , biology , mathematics , statistics , gene , sociology
Objective: To determine whether previously identified adult obesity susceptibility loci were associated uniformly with childhood BMI across the BMI distribution. Design and 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 ). Conclusion: 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.