Gene Variants Have Small Effect on Weight-Loss Success in Kids

By Anne Harding

December 19, 2020

NEW YORK (Reuters Health) - Genes don't have a big effect on whether or not lifestyle interventions for treating obesity in children will succeed, new findings suggest.

Five of 56 single-nucleotide variants (SNV) linked to obesity in children were associated with how much weight children lost during an in-hospital lifestyle intervention, but their effect size was small, Dr. Melanie Heitkamp of the Technical University of Munich, in Germany, and her colleagues found.

"Genes appear to play a minor role in weight reduction by lifestyle intervention in children with overweight and obesity," Dr. Heitkamp told Reuters Health by email. "Environmental, social and behavioral factors are more important to consider in obesity treatment strategies."

In the LOGIC study, Dr. Heitkamp and her team enrolled 1,429 overweight or obese children in a lifestyle intervention lasting four to six weeks that included daily physical activity, a calorie-restricted diet and behavioral therapy. Genotyping was performed in 908 children using the Cardio-MetaboChip (Illumina), while 290 were genotyped with the MassARRAY system with iPlex chemistry (Agena).

Mean weight loss was 8.7 kg, while BMI decreased by 3.3, the team reports in JAMA Pediatrics.

Children homozygous for the rs7164727 and rs12940622 risk alleles lost 0.42 and 0.35 fewer kilograms, respectively, than those without these variants, the researchers found.

The variants rs13201877, rs10733682 and rs2836754 were associated with greater weight loss, with carriers losing 0.65 kg, 0.45 and 0.56 kg more, respectively, than those without the risk alleles.

"Distinguishing individuals who are more likely or unlikely to respond to obesity treatment based on their genetic predisposition may not necessarily lead to better treatment success," Dr. Heitkamp said. "Even individuals who carry the risk alleles of the obesity-related genes will benefit from a healthy lifestyle including an energy-balanced diet and regular physical activity."

She concluded: "There is a need for further large-scale studies to investigate the effect of multiple obesity-associated genetic variants."

Dr. Ann Chen Wu of Harvard Medical School in Boston co-authored an editorial accompanying the study.

"To me, the take-home message is that genetic loci can help inform precision treatment of childhood obesity," she told Reuters Health by email, noting that the findings require validation.

She added: "In our editorial, we suggest that this study is a major step towards precision treatment for childhood obesity, however, many more than five genetic loci will be needed to have true clinical impact on obesity management. For additional loci to be discovered, we will need the development of more statistical tools. With the five genetic loci studies, the change in weight was less than 0.7 kg. This suggests that lifestyle interventions are just as important, possibly more important, than genes."

SOURCE: and JAMA Pediatrics, online December 14, 2020.