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Tracing genes linked to obesity
January 28, 2018, 4:23 pm

It is not just diet and physical activity, your genes too play a part in determining how easily you might lose or gain weight.

Researchers affiliated with the Genetic Investigation of Anthropometric Traits (GIANT) consortium, an international collaboration among various health institutions, have found 13 genes that carry variations associated with body mass index (BMI).

In the past decade, researchers in the GIANT consortium have performed genome-wide screens in hundreds of thousands of individuals to identify genetic variations associated with obesity and BMI. However, until now, the genetic variations they identified were merely ‘flags’ on the genome that highlighted DNA sequences of interest.

In this new, first ever large-scale study to pinpoint genetic variations that may directly impact the function of the genes, researchers focused on a specific set of genetic variations that are likely to affect the function of genes and their proteins — an approach that expedited the discovery of the causal genes that affect body weight.

The new study, an international collaboration that involved more than 250 research institutions, combined genetic data from more than 700,000 individuals and 125 different studies to form the largest genetic association study to date. The researchers identified 14 genetic variations in 13 genes, including a risky copy variation — a phenomenon in which sections of the genome are repeated — that causes carriers to weigh over seven kilos more, on average, than individuals who do not carry the variation.

The implicated risky copy variation gene is called MC4R and approximately 1 in 5,000 individuals carry this risk copy, which causes the gene not to produce any of the protein needed to inform the brain to stop eating. While this variant was identified two decades ago in individuals with extreme and early-onset obesity, the new study shows that it also affects body weight in the general population.

Furthermore, the researchers identified two variants that may affect the function of a gene called GIPR. Approximately 1 in 400 individuals carry a protective copy of either variant and they tend to weigh an average of two kilos less than non-carriers. Eight of the 13 genes identified were newly implicated in obesity, and researchers said these genes will require further follow-up to understand the mechanisms through which they affect body weight.

By knowing the genes and the biological pathways through which they work, researchers believe they are a few steps closer to understanding why some people gain weight more easily than others, which is critical for developing effective treatments. But further research on each of the identified genes is needed to understand the mechanisms through which they act, before potential targets for therapeutic interventions, and personalized treatment for carriers of the genetic variations, could be developed, said the research team.

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