Severe obesity linked to newly identified gene mutations

January 8, 2018, Imperial College London
Credit: CC0 Public Domain

Researchers have discovered mutations in a gene related to obesity, offering new treatment possibilities in the fight against the global epidemic.

Research into the genetic causes of , and related conditions, could be incredibly valuable in finding ways to treat them. Currently, there are some drugs available or being tested, but knowing what specific mutations cause obesity allows scientists to create drugs that target them specifically.

The new study, led by Imperial College London and published today in Nature Genetics, focussed on children suffering from obesity in Pakistan, where genetic links to obesity had been previously identified by the team in about 30% of cases.

This link of to obesity is due to that are more likely to be inherited and passed on to children in a region like Pakistan because of the high level of consanguinity (inter-family relationships) in its population. This is because parents who are closely related are more likely to be carrying the same mutation, so a child may inherit from both sides, causing the mutation to take effect.

This new study used genome sequencing and found mutations in one specific gene related to obesity: adenylate cyclase 3 (ADCY3). When mutations occur in ADCY3, the protein it codes for forms abnormally and doesn't function properly. This leads to abnormalities relating to appetite control, diabetes, and even sense of smell.

Professor Philippe Froguel, chair of Genomic Medicine at Imperial, said: "Early studies into ADCY3 tested mice that were bred to lack that gene, found that these animals were obese and also lacked the ability to smell, known as anosmia. When we tested our patients, we found that they also had anosmia, again showing a link to mutations in ADCY3."

ADCY3 is thought to impact a system that links the hypothalamus (part of the brain) to the production of hormones that regulate a wide variety of biological functions, including appetite.

After identifying the mutations in the Pakistani patients, the researchers entered their results into GeneMatcher, described by Professor Froguel as a "dating agency for genetics". This led to another group of scientists in the Netherlands contacting the team with their own ADCY3 findings in one of their patients with obesity.

This new European patient inherited different mutations on the same ADCY3 gene from both parents (as they were not closely related, as in Pakistan) so the ADCY3 gene of the offspring was not functioning properly, leading to obesity.

Further connections were made with a group of Danish scientists, studying the Inuit population of Greenland. Whilst not traditionally consanguineous (as in close family marriages), this population is small, so inbreeding is likely to have occurred.

This research also found a link between ADCY3 and obesity, and is published alongside the Imperial research in Nature Genetics. Professor Froguel noted how positive this kind of collaboration is, particularly in terms of showing that the research and findings are reproducible.

Professor Froguel added: "Obesity is not always gluttony, as is often suggested, and I think we should have a positive outlook considering the new treatments that are becoming possible. Such attempts to understand obesity and look for a cure are a real strength of the Imperial Faculty and Department of Medicine."

Explore further: New genetic form of obesity and diabetes discovered

More information: Sadia Saeed et al, Loss-of-function mutations in ADCY3 cause monogenic severe obesity, Nature Genetics (2018). DOI: 10.1038/s41588-017-0023-6

Related Stories

New genetic form of obesity and diabetes discovered

June 30, 2015
Scientists have discovered a new inherited form of obesity and type 2 diabetes in humans.

Intellectual disabilities caused by protein defect

September 4, 2017
Intellectual disabilities are often caused by a mutation that damages a gene, preventing the associated protein from functioning properly. However, a mutation can also change the function of a gene. As a result, the gene ...

Genetic study links body clock receptor to diabetes

January 29, 2012
A study published in Nature Genetics today has found new evidence for a link between the body clock hormone melatonin and type 2 diabetes. The study found that people who carry rare genetic mutations in the receptor for melatonin ...

Recommended for you

Analytical tool predicts genes that can cause disease by producing altered proteins

July 19, 2018
Predicting genes that can cause disease due to the production of truncated or altered proteins that take on a new or different function, rather than those that lose their function, is now possible thanks to an international ...

Childhood stress leaves lasting mark on genes

July 18, 2018
Kids who experience severe stress are more likely to develop a host of physical and mental health problems by the time they reach adulthood, including anxiety, depression and mood disorders. But how does early life stress ...

Study shows DNA methylation related to liver disease among obese patients

July 18, 2018
DNA methylation is a molecular process that helps enable our bodies to repair themselves, fight infection, get rid of environmental toxins, and even to think. But sometimes this process goes awry.

Protein found to be key component in irregularly excited brain cells

July 17, 2018
In a new study in mice, researchers have identified a key protein involved in the irregular brain cell activity seen in autism spectrum disorders and epilepsy. The protein, p53, is well-known in cancer biology as a tumor ...

World's largest study on allergic rhinitis reveals new risk genes

July 17, 2018
An international team of scientists led by Helmholtz Zentrum München and University of Copenhagen has presented the largest study so far on allergic rhinitis in the journal Nature Genetics. The data of nearly 900,000 participants ...

New platform poised to be next generation of genetic medicines

July 16, 2018
A City of Hope scientist has discovered a gene-editing technology that could efficiently and accurately correct the genetic defects that underlie certain diseases, positioning the new tool as the basis for the next generation ...

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.