Genetic risk profiles for a childhood with severe overweight

Pediatr Obes. 2014 Aug;9(4):272-80. doi: 10.1111/j.2047-6310.2013.00166.x. Epub 2013 Apr 29.


Objective: The objective of this study was the description of a valid genetic risk score (GRS) to predict individuals with high susceptibility to childhood overweight by their genetic profiles.

Design and methods: Case-control study including a group of children with high-risk familial predisposition to morbid obesity. Birth cohort from general population constituted the validation sample. For the discovery sample, 218 children with non-syndromic obesity and 190 control individuals were included. The validation sample was 653 children from two birth cohorts belonging to the INMA (Infancia y Medio Ambiente [Environment and Childhood] )project. 109 SNPs located in the genes FTO, SEC16B, BDNF, ETV5, SH2B1, GNPDA2, LYPLAL1, MSRA, TFAP2, KCTD15, MTCH2 and NEGR1, previously reported in association to body mass index (BMI) were analysed. For the validation sample, association between genome-wide data and BMI measurements between 3.5 and 5 years of age, were evaluated.

Results: The GRS includes six SNPs in the genes FTO, TFAP2B, SEC16B, ETV5 and SH2B1. The score distribution differs among cases and controls (P = 9.2 × 10(-14) ) showing a significant linear association with obesity (odds ratio [OR] per allele = 1.69; confidence interval [CI] 95% = 1.46-1.97; P = 4.3 × 10(-1) and area under the receiver operating characteristic curve [AUC] = 0.727; CI 95% = 0.676-0.778). The results were validated by the INMA cohort (OR per allele = 1.23 CI 95% = 1.03-1.48 and AUC = 0.601 CI 95% = 0.522-0.680).

Conclusions: The use of our proposed genetic score provides useful information to determine those children who are susceptible to obesity. To improve the efficiency of clinical prevention and treatment of obesity, it is essential to design individualized based protocols in advance knowledge of the molecular basis of inherited susceptibility.

Keywords: Obesity; SNP; inherited risk; score.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Algorithms
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Body Mass Index
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Clinical Protocols
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Models, Genetic
  • Pediatric Obesity / epidemiology
  • Pediatric Obesity / genetics*
  • Pediatric Obesity / prevention & control
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics
  • Risk Factors
  • Transcription Factor AP-2 / genetics
  • Transcription Factors / genetics


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • ETV5 protein, human
  • Proteins
  • SEC16B protein, human
  • SH2B1 protein, human
  • TFAP2B protein, human
  • Transcription Factor AP-2
  • Transcription Factors
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human