Obesity Genes and Weight Loss During Lifestyle Intervention in Children With Obesity

Abstract

Importance: Genome-wide association studies have identified genetic loci influencing obesity risk in children. However, the importance of these loci in the associations with weight reduction through lifestyle interventions has not been investigated in large intervention trials.

Objective: To evaluate the associations between various obesity susceptibility loci and changes in body weight in children during an in-hospital, lifestyle intervention program.

Design, setting, and participants: Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children (LOGIC), an interventional prospective cohort study, enrolled 1429 children with overweight or obesity to participate in an in-hospital lifestyle intervention program. Genotyping of 56 validated obesity single-nucleotide variants (SNVs) was performed, and the associations between the SNVs and body weight reduction during the intervention were evaluated using linear mixed-effects models for each SNV. The LOGIC study was conducted from January 6, 2006, to October 19, 2013; data analysis was performed from July 15, 2015, to November 6, 2016.

Exposures: A 4- to 6-week standardized in-hospital lifestyle intervention program (daily physical activity, calorie-restricted diet, and behavioral therapy).

Main outcomes and measures: The association between 56 obesity-relevant SNVs and changes in body weight and body mass index.

Results: Of 1429 individuals enrolled in the LOGIC Study, 1198 individuals (mean [SD] age, 14.0 [2.2] years; 670 [56%] girls) were genotyped. A mean (SD) decrease was noted in body weight of -8.7 (3.6) kg (95% CI, -15.7 to -1.8 kg), and body mass index (calculated as weight in kilograms divided by height in meters squared) decreased by -3.3 (1.1) (95% CI, -5.4 to -1.1) (both P < .05). Five of 56 obesity SNVs were statistically significantly associated with a reduction of body weight or body mass index (all P < 8.93 × 10-4 corresponding to Bonferroni correction for 56 tests). Compared with homozygous participants without the risk allele, homozygous carriers of the rs7164727 (LOC100287559: 0.42 kg; 95% CI, 0.31-0.53 kg, P = 4.00 × 10-4) and rs12940622 (RPTOR: 0.35 kg; 95% CI, 0.18-0.52 kg; P = 1.86 × 10-5) risk alleles had a lower reduction of body weight, whereas carriers of the rs13201877 (IFNGR1: 0.65 kg; 95% CI, 0.51-0.79 kg; P = 2.39 × 10-5), rs10733682 (LMX1B: 0.45 kg; 95% CI, 0.27-0.63 kg; P = 6.37 × 10-4), and rs2836754 (ETS2: 0.56 kg; 95% CI, 0.38-0.74 kg; P = 1.51 × 10-4) risk alleles were associated with a greater reduction of body weight after adjustment for age and sex.

Conclusions and relevance: Genes appear to play a minor role in weight reduction by lifestyle in children with overweight or obesity. The findings suggest that environmental, social, and behavioral factors are more important to consider in obesity treatment strategies.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. Flowchart

LOGIC indicates Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children.

Figure 2.. Changes in Body Weight and Genotypes

Mean change in age- and sex-adjusted body weight between weeks 0 and 6 and week 0 for carriers of the different genotypes of the SNVs rs13201877 (A), rs10733682 (B), rs7164727 (C), rs12940622 (D) and rs 2836754 (E). A indicates adenosine; C, cytosine; G, guanine; and T, thymine. Parenthetical values indicate the number of children included in the analysis. Error bars indicate the 95% CI.

Figure 3.. Changes in Body Mass Index (BMI) and Genotypes

Mean change in age- and sex-adjusted BMI (calculated as weight in kilograms divided by height in meters squared) between weeks 0 and 6 and week 0 for carriers of the different genotypes of the SNVs rs13201877 (A) and rs2836754 (B). A indicates adenosine; C, cytosine; G, guanine; and T, thymine. Parenthetical values indicate the number of children included in the analysis. Error bars indicate the 95% CI.