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Original Investigation
December 14, 2020

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

Author Affiliations
  • 1Department of Prevention and Sports Medicine, Centre for Sports Cardiology, University Hospital “Klinikum rechts der Isar,” Technical University of Munich, Munich, Germany
  • 2Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
  • 3German Center for Diabetes Research, Helmholtz Zentrum München, Neuherberg, Germany
  • 4Now with Roche Diagnostics, Bavaria, Germany
  • 5Rehabilitation Clinic “Klinik Schönsicht,” Berchtesgaden, Germany
  • 6German Center for Cardiovascular Research, partner site Munich Heart Alliance, Munich, Germany
JAMA Pediatr. 2021;175(1):e205142. doi:10.1001/jamapediatrics.2020.5142
Key Points

Question  Are genes associated with obesity treatment success in children with obesity?

Findings  In this interventional genetic association study that included 1198 children with overweight or obesity, 5 of 56 obesity single-nucleotide variants were statistically significantly associated with changes in body weight, however, only to a minor degree.

Meaning  In this study, environmental, social, and behavioral factors seem to play a substantial role in obesity treatment strategies in children.


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.

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    1 Comment for this article
    Perhaps calorie restriction is the wrong intervention
    Stanley Sokolow, DDS | Retired.
    This study should be interpreted cautiously. Calorie-restricted diets, as used in this study, haven't been as effective at weight reduction as carbohydrate-restricted diets have been in clinical trials on adults. Isocaloric diet trials comparing calorie restriction versus carbohydrate restriction (making up the missing carb calories with increased fats) have shown rapid and sustained weight loss without loss of lean body mass, without hunger. Carbohydrate load seems to have a much stronger interaction with the epigenome than simple calorie restriction does.