Obesity rare in rural children despite genetic susceptibility: study

Prevalence of underweight children was more rural schools, while obese children were from urban schools

A genetic study of childhood obesity in about 6,400 school-going children aged 9-18 years has found that socioeconomic status significantly modulates the inherent genetic susceptibility to obesity. Unlike in the case of adult obesity, genetic studies to understand obesity in children and adolescents are limited, particularly in non-Caucasian populations. Besides identifying the genetic variants associated with childhood obesity in the Indian population, a study undertaken by a clutch of Indian institutions led by researchers from the School of Biotechnology in JNU, Delhi has studied how socioeconomic status modifies the genetic susceptibility to obesity. The study has been accepted for publication in the journal Obesity.

The researchers performed a two-staged Genome-wide Association Study (GWAS) on 5,673 children and an independent Exome-wide Association Study (ExWAS) on 4,963 children to identify the genetic variants associated with childhood obesity. “While GWAS examines the entire genome for common genetic variants linked to a trait, often focusing on the non-coding regions, the EWAS focuses specifically on rare variants in the protein-coding regions (exome),” explains Janaki M. Nair from JNU and the first author of the paper. “Combining the two approaches offers a more comprehensive understanding of the genetic basis of obesity.” The GWAS was performed in two stages — the discovery phase on 1,510 children and the replication phase on 4,555 children. “The discovery phase involves a genome-wide scan to identify variants associated with obesity, while the replication phase validates the lead associations in the discovery phase in an independent sample set,” she says.

Besides two genes known to be associated with obesity, the GWAS helped identify six novel associations in genes. Potential functional roles of the identified novel genes were evaluated using gene-expression profiles in different human tissues, and gene-regulatory data from publicly available databases. “Most of the identified genes showed the highest expression in adipose tissue,” Ms. Nair says. “Among the newly identified genetic variants, one (TCF7L2) functions as an enhancer in obesity-related tissues, while another gene (CDC5L) plays a role in regulating adipose tissue metabolism. A third gene (SNTG1) influences triglyceride levels, while the effect of another gene (MX1) is mediated through thyroid-related pathways, and two genes (IMMP2L and IPMK) impact the hunger-satiety signalling via the leptin-melanocortin pathway.”

Besides validating the association of known genes involved in obesity in the Indian population, the exome-wide association study identified four novel missense variants for BMI, body weight and waist-to-hip ratio. “The involvement of these identified genes in key obesity-associated pathways further strengthens the significance of our findings, highlighting their potential role in obesity and related metabolic disorders,” she says.

“Since genetic factors alone do not fully explain the development of childhood obesity, we studied the role of socioeconomic status in shaping obesity. Our study revealed significant associations between school types — students from urban private schools, urban government schools and rural government schools — which is an indicator of socioeconomic status and BMI in children,” says Dr. Dwaipayan Bharadwaj from JNU and one of the corresponding authors. “As expected, the study found that children from lower socioeconomic status showed a higher prevalence of underweight, while those from higher socioeconomic status faced a higher prevalence of obesity.” While children from urban private schools consumed more processed food and led a sedentary lifestyle, rural children led an active lifestyle and lacked access to quality nutrition. 

The study found that socioeconomic status greatly influenced genetic susceptibility to obesity. For each genetic variant significantly linked to obesity in the study population, children were grouped by genotype and their BMI (adjusted for age and sex) compared across rural, urban government, and urban private schools. “Despite the frequency of risk genotypes and the variant effects being consistent across three categories, children from urban private schools tend to have higher BMI compared to children from urban government or rural schools,” Ms. Nair says. “Even with similar genetic risks, children belonging to high SES were more likely to be obese, emphasising the powerful gene-environment interaction.”