Scientists Find New Genetic Variant in Largest-ever Study of Childhood Obesity Across Ethnic Groups

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by Joana Carvalho |

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By looking at the genetic backgrounds of nearly 30,000 individuals from different ethnic groups, scientists have identified a new genetic variant associated with childhood obesity and confirmed 18 others.

Results from the study with that finding, “A Trans-ancestral Meta-Analysis of Genome-Wide Association Studies Reveals Loci Associated with Childhood Obesity,” were published in Human Molecular Genetics.

Obesity is a highly variable disorder resulting from a combination of genetic, environmental, and lifestyle factors. Statistics estimate that up to 70% of its variation is due to individual differences in genetic backgrounds.

“Large-scale genome-wide association studies (GWAS) have now reported many hundreds of  loci associated with BMI [body mass index]/obesity in adults, and principally in populations of European ancestry,” the researchers wrote.

GWAS are based on a method that scans the entire genome — the genes present in our DNA — looking for specific types of genetic alterations found more frequently in people with a particular disease. Genetic loci refer to the location of a gene inside a chromosome.

However, very little is known about the genetic causes of obesity in children, especially among individuals of non-European origin.

In this study, an international group of researchers reported the findings of the largest meta-analysis study to date that attempts to pinpoint the genetic causes of childhood obesity.

The study, which was part of the Early Growth Genetics (EGG) Consortium, included data from 30 GWAS studies containing information from 13,005 obese individuals and 15,599 healthy subjects (controls) of European, African, North/South American, and East Asian origin.

Individuals were considered obese if their BMI was beyond the 95th percentile of BMI before they reached the age of 18 years old, following the criteria defined by the U.S. Centers for Disease Control and Prevention (CDC).

Besides looking for new genetic variants that could be implicated in childhood obesity, researchers also sought to validate other genes that had been reported previously to be involved in obesity and BMI and likely also played a role in childhood obesity. Information from these genes was obtained from a replication study involving 1,888 obese individuals and 4,689 controls of European and North/South American origin.

Analyses confirmed the 18 gene variants previously described were associated with childhood obesity or BMI. Besides validating these loci, the team identified a new genetic variant (rs10835310) associated with childhood obesity located near the METTL15 gene. This variant was associated only with childhood obesity in European people, but showed a similar trend for other ethnic groups.

Investigators then performed a fine-mapping analysis of four of these genes — FAIM2, GNPDA2, MC4R and SEC16B — to narrow the mutations associated with childhood obesity. The analysis revealed fewer than 10 single nucleotide (the building blocks of DNA) substitutions were driving the association in these genes.

“As we continue to deepen our research into the genetics of obesity, this knowledge is bringing us closer to pinpointing specific causal genes and how they function in giving rise to obesity,” Struan F.A. Grant, PhD, said in a press release. Grant is director of the Center for Spatial and Functional Genomics (CSFG) at Children’s Hospital of Philadelphia, and lead author of the study,

“We have also shown that childhood is genetically very similar to adult BMI and with far greater numbers of samples we would most likely see more significant loci in common with the two [forms of obesity]. As such, we have gained greater insights in the biology of obesity in the pediatric setting and these loci warrant further functional follow up in order to provide greater potential therapeutic insights,” they wrote.

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