Through the sequencing of more than 640,000 human exomes, researchers identify rare gene coding variants strongly associated with body mass index (BMI) - including the variant GPR75, which conferred protection from obesity in mouse models. Not only do the findings provide potential therapeutic targets for treating obesity, but they also demonstrate the power and versatility of massive-scale exome sequencing in discovering rare coding variants that could offer new and potentially translatable biological functions.
Body fat is a highly heritable trait and the obesity to which body fat contributes is linked to a variety of human diseases, including diabetes, cancer, and heart disease. While it's known that genetic factors play an essential role in energy balance and body fat regulation, how genes and rare coding variants can predispose or protect individuals from obesity is not fully understood. Understanding this could provide a pathway to developing safe and effective therapeutic strategies for treating obesity.
The researchers sequenced the exomes of 645,626 individuals from the United Kingdom, United States and Mexico and discovered a set of 16 genes in which rare coding variants exhibited an exome-wide significant association with BMI.
One of these, GPR75 - a brain-expressed G protein-coupled receptor - was observed in roughly 4 out of every 10,000 sequenced individuals and associated with lower BMI. Knock-out of this gene in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet.
"The principles of discovery exemplified in the study of the authors. go beyond that of body weight control and obesity," write the authors in a related Perspective. "It is likely that human exome sequencing at scale will become an increasingly important entry point for the discovery of mechanistic insights into mammalian biology."
https://science.sciencemag.org/content/373/6550/eabf8683
Gene variants linked to human obesity
- 2,602 views
- Added
Edited
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
Gene to regulate sleep!
Read more
Why do we still have mitochondrial DNA?
Read more
New mathematical model to explain human genome mutation variability
Read more
Mutation in bile acid receptor identified!
Read more
A gene associated with a set of poorly understood rare diseases ide…
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar