New genomic technique reveals obesity gene variants

Nov 29, 2010

Obesity is highly heritable, but so far genetic association studies have only explained a small fraction of this heritability. Now, in a study published in BioMed Central's open access journal Genome Biology, researchers have identified DNA variants in two nervous system genes that are associated with an excessively high BMI.

Kelly Frazer and colleagues from UC San Diego, Scripps Translational Science Institute and Sanofi-Aventis used a new approach that is likely to become popular in searching for hidden : the resequencing of a candidate area of the genome in a large number of individuals followed by screening for within this region that are associated with the disease or condition in question.

Frazer said, "We sequenced two intervals encoding the enzymes FAAH and MGLL which modulate the levels of endocannabinoids present in the brain and peripheral tissues that are involved in the regulation of and appetite. The level of these endocannabinoids is high in obese patients, and thus these two enzymes provide strong candidates to examine for a genetic association with ".

In these two genes, the researchers were able to identify four regions associated with BMI: the FAAH promoter, MGLL promoter, MGLL intron 2, and an enhancer in the MGLL intron 3. Further testing of one of these regions revealed rare variants that were associated with increased levels of endocannabinoids in the plasma, which is consistent with previous findings.

According to Frazer, "This is one of the first studies to use the new sequencing technologies to link rare and low frequency variants to a complex trait such as obesity and will be of particular interest to understand more comprehensively the role of inheritance in obesity, a rapidly rising serious health issue across the world".

Explore further: Assortativity signatures of transcription factor networks contribute to robustness

More information: Population sequencing of two endocannabinoid metabolic genes identifies rare and common regulatory variants associated with extreme obesity and metabolite level, Olivier Harismendy, Vikas Bansal, Gaurav Bhatia, Masakazu Nakano, Michael Scott, Xiaoyun C Wang, Colette Dib, Edouard Turlotte, Jack C Sipe, Sarah S Murray, Jean-Francois Deleuze, Vineet Bafna, Eric J Topol and Kelly A Frazer, Genome Biology (in press), genomebiology.com/

add to favorites email to friend print save as pdf

Related Stories

Large-scale analysis identifies 32 genetic loci for obesity

Oct 11, 2010

An international team of researchers has identified 18 new genetic loci associated with obesity assessed by BMI, and confirmed a link between obesity and 14 previously known loci. Almost 250,000 individuals were included ...

Brain background to body mass

Dec 14, 2008

A genetic study of more than 90,000 people has identified six new genetic variants that are associated with increased Body Mass Index (BMI), the most commonly used measure of obesity. Five of the genes are known to be active ...

Human Genome Project is 10: Where are we now?

Mar 02, 2010

"It's hard to think back and remember how we worked then. We were scrabbling around in the dark," says Professor Mark McCarthy of the Oxford Centre for Diabetes, Endocrinology and Metabolism [OCDEM], recalling ...

Recommended for you

Mutation disables innate immune system

22 hours ago

A Ludwig Maximilian University of Munich team has shown that defects in the JAGN1 gene inhibit the function of a specific type of white blood cells, and account for a rare congenital immune deficiency that ...

Study identifies genetic change in autism-related gene

Aug 28, 2014

A new study from Bradley Hospital has identified a genetic change in a recently identified autism-associated gene, which may provide further insight into the causes of autism. The study, now published online in the Journal of ...

NIH issues finalized policy on genomic data sharing

Aug 27, 2014

The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products and procedures that improve health while ...

The genes behind the guardians of the airways

Aug 27, 2014

Dysfunctions in cilia, tiny hair-like structures that protrude from the surface of cells, are responsible for a number of human diseases. However the genes involved in making cilia have remained largely elusive. ...

User comments : 0