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Genetic susceptibility to childhood obesity moderated by cumulative stress

Tristan Manalac
11 Jul 2018

Cumulative stress appears to interact with polygenic susceptibility for elevated body mass index (BMI), according to a recent China study.

“Our findings were generally consistent with the differential susceptibility perspective, showing that children carrying additional BMI-raising alleles are at heightened risk of obesity when experiencing cumulative stress, however, the very BMI-raising alleles seem to confer protection against obesity in the absence of chronic stress,” said researchers.

The study included 421 boys (mean BMI, 19.04±3.39 kg/m2) and 579 girls (mean BMI, 18.32±2.95 kg/m2). The average age and BMI in the entire cohort was 8.97±0.85 years and 18.62±3.16 kg/m2, respectively. [Int J Obes 2018;42:1177-1184]

Hair cortisol concentration (HCC) was significantly associated with BMI only in children in the highest tertile of polygenic susceptibility scores (PSS; r=0.269; p<0.001). Moreover, HCC and PSS exhibited a significant interaction with BMI (t=3.92; p<0.001).

Notably, among children with cumulative stress exposure (defined as being in the highest quartile of HCC), BMI was significantly higher in children belonging to the highest vs lowest PSS group (19.97±3.54 vs 18.59±3.45 kg/m2; p=0.02).

Among participants without cumulative stress, the trend was significant in the opposite direction (BMI of highest vs lowest PPS group: 17.53±2.49 vs 18.64±3.03 kg/m2; p=0.021).

This was confirmed in subsequent analyses. When children with the highest PSS scores experienced cumulative stress, BMI was significantly elevated compared with their counterparts who had the lowest PSS scores (β=1.46; 95 percent CI, 0.63–2.29; p=0.001).

The opposite pattern was true for children without cumulative stress, such that those with the highest PPS scores showed significantly lower BMI than those with the lowest PPS scores (β=–1.27; –2.17 to –0.38; p=0.001).

“To our knowledge, this report is the first to document polygenic interaction with chronic stress exposure in the aetiology of child obesity,” said researchers, noting that the observed interactions remained statistically significant even after adjusting for obesogenic lifestyle risk factors.

“The present analyses indicate that chronic stress may act as an important environmental trigger, but only for children carrying multiple BMI-associated loci identified in [genome-wide association studies] who are more sensitive to favourable and unfavourable psychosocial environment than those without these genetic makeups,” they added.

While the mechanisms underlying the relationship between cumulative stress and genetic susceptibility have not yet been identified in the literature, “[i]t is believed that cumulative stress exposure might degrade physiological function, triggering a cascade of weight gain-inducing effects,” researchers explained.

Moreover, some common genetic variants related to BMI gain have been shown to exert their effects through the disruption of appetite control and energy balance. Thus, children who carry these variants “may be more affected under cumulative stress exposure compared to children with less genetic sensitivity,” they noted.

For the present study, researchers extracted DNA from buccal cheek swabs and subjected the samples to genotyping analysis. Eleven single-nucleotide polymorphisms associated with childhood BMI were selected for the calculation of the PSS. Enzyme-linked immunosorbent assays were used to measure HCC levels from processed hair samples.

“[F]urther research in how genes and psychosocial environment can moderate each other will be needed to fully understand this complex relationship and to use it as a robust evidence-base for health policy,” said researchers.

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Most Read Articles
Roshini Claire Anthony, 12 Apr 2018

Individuals with severe obesity who undergo Roux-en-Y gastric bypass (RYGB) may have a higher risk of nonvertebral fractures than those who undergo adjustable gastric banding (AGB), according to a study presented at the recent ENDO 2018 sessions.