Large-scale study to pinpoint genes linked to obesity

January 10, 2018, The Mount Sinai Hospital
Credit: CC0 Public Domain

It's not just diet and physical activity; your genes also determine how easily you lose or gain weight. In a study published in the January issue of Nature Genetics, researchers at the Icahn School of Medicine at Mount Sinai and other institutions of the Genetic Investigation of Anthropometric Traits (GIANT) consortium found 13 genes that carry variations associated with body mass index (BMI). This was the first large-scale study to pinpoint genetic variations that may directly impact the function of the genes.

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. Until now, the genetic variations they identified were merely "flags" on the genome that highlighted DNA sequences of interest. In this new study, however, the consortium focused on a specific set of genetic variations that are likely to affect the function of and their proteins—an approach that expedited the discovery of the causal genes that affect .

Led by Ruth Loos, PhD, professor at The Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai, and Joel Hirschhorn, MD, PhD, Concordia Professor of Pediatrics and Professor of Genetics at Boston Children's Hospital and Harvard Medical School, and co-director of the Broad Institute Metabolism Program, the study was an international collaboration involving more than 250 research institutions. Genetic data from more than 700,000 individuals and 125 different studies were combined 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 15 pounds more, on average, than individuals who do not carry the variation. The gene is called MC4R and approximately 1 in 5,000 individuals carries 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 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 carries a protective copy of either variant and they tend to weigh an average of 4.5 pounds less than non-carriers. Eight of the 13 genes identified were newly implicated in obesity and will require further follow-up to understand the mechanisms through which they affect body weight.

"Our study has identified genes that play a crucial role in the neuronal control of body weight. They act in the brain in pathways that may affect people's food intake, hunger, satiety, etc. Individuals who inherit these genetic variations may find it harder to eat less or stop eating, as compared to those who did not inherit these variations," said Dr. Loos. "It is also the first time a genetic association study for BMI identifies genes that act in pathways that affect energy expenditure and fat cell biology."

The investigators used computational analysis to further hone in on genes that likely play a key role in obesity. "By considering the genes as a group rather than one-by-one, we could highlight specific genes that both had strong support from genetics and that likely carry out functions that we predict to be important in controlling body weight," said Joel Hirschhorn, MD, PhD, Concordia Professor of Pediatrics and Professor of Genetics at Boston Children's Hospital and Harvard Medical School, Co-Director of the Metabolism Program at the Broad Institute and the GIANT consortium.

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.

"Our study has provided new potential targets for therapeutic interventions, and may even help personalize treatment for carriers of the genetic variations. While we are a few steps closer to understanding the biology of why some people gain or lose weight more easily than others, further research on each of the identified genes is needed to understand the mechanisms trough which they act," noted Dr. Loos.

Other institutions involved in this study include the Eli and Edythe L. Broad Institute of the Massachusetts Institute of Technology and Harvard. Financial support for the international collaboration was provided in part by the National Institutes of Health.

Explore further: Largest ever genome-wide study strengthens genetic link to obesity

More information: undefined undefined et al. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity, Nature Genetics (2017). DOI: 10.1038/s41588-017-0011-x

Related Stories

Largest ever genome-wide study strengthens genetic link to obesity

February 11, 2015
There are many reasons why people gain different amounts of weight and why fat becomes stored in different parts of their bodies. Now researchers are homing in on genetic reasons. Their findings, part of the largest genome-wide ...

Researchers find genes may 'snowball' obesity

December 7, 2017
There are nine genes that make you gain more weight if you already have a high body mass index, McMaster University researchers have found.

Physical activity helps to counteract weight gain from obesity-causing gene variant

April 27, 2017
Physical activity can reduce the weight-gaining effects of the genetic variant that carries the greatest risk of obesity, report Mariaelisa Graff of the University of North Carolina at Chapel Hill, Tuomas Kilpeläinen of ...

Gene variants may play role in obesity

June 17, 2013
(HealthDay)—Two new studies offer some solace to those who can't control their weight despite diet and exercise by providing more evidence that genetics may play a role in obesity.

Obesity genes identified by worldwide research team

February 24, 2015
A massive worldwide analysis of genetic data from almost 340,000 people around the world has brought understanding of the genetic basis of obesity a step closer.

Variations in gene expression may underlie increased food intake in obesity

April 11, 2016
Large-scale genetic studies have identified a number of variations in genes that increase an individual's susceptibility to obesity.

Recommended for you

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.