An international consortium of scientists has analyzed protein-coding genes from nearly 46,000 people, linking rare DNA alterations to type 2 diabetes. The study, one of the largest known of its type, includes data from people of European, African American, Hispanic/Latino, East Asian, and South Asian ancestries.
From this large cohort--roughly 21,000 individuals with type 2 diabetes and 25,000 healthy controls--the researchers identified four genes with rare variants that affect diabetes risk. The data suggests that hundreds more genes will likely be identified in the future.
These genes and the proteins they encode are potential targets for new medicines, and may guide researchers to better understand and treat disease.
All of the team's results are publicly available online through the Type 2 Diabetes Knowledge Portal, enabling scientists around the world to access and use the information for their own research.
"These results demonstrate the importance of studying large samples of individuals from a wide range of ancestries," said senior study author. "Most large population studies focus on individuals of European ancestry, and that can make it hard to generalize the results globally. The more diverse the cohort makes for better, more informative science."
"We now have an updated picture of the role of rare DNA variations in diabetes," said the first author on the study. "These rare variants potentially provide a much more valuable resource for drug development than previously thought. We can actually detect evidence of their disease association in many genes that could be targeted by new medications or studied to understand the fundamental processes underlying disease." The study was published today in Nature.
For this study, the researchers sequenced what's called the "exome," that is, only those regions in the genome that code for proteins.
Another approach to finding disease-associated variants is called a genome wide association study, or GWAS. This approach can be very effective for finding common-disease variants throughout the entire genome, but can miss the less-common exome variants. And this is key, because while rare exome variants are extremely hard to detect, they can provide invaluable insight into disease-related genes, which in turn can suggest new drug targets.
For this reason, the researchers aim to increase sample sizes in future studies. With a cohort of almost 50,000, this may be the largest exome sequencing study of type 2 diabetes, but as the authors state in the paper, sample sizes ranging between 75,000 and 185,000 cases may be needed to identify even those rare variants with the largest impact.
"It's critical to remember that just because we are examining variants in protein-coding DNA, we don't get a break on the number of samples needed to detect a significant effect," says the author. "The effects of these variations can be powerful, but because they are so rare, we still need to increase the sample size in order to really derive compelling insights."
https://www.broadinstitute.org/news/massive-sequencing-study-links-rare-dna-alterations-type-2-diabetes
https://www.nature.com/articles/s41586-019-1231-2
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fexome-sequencing-of-20&filter=22
Latest News
Colorectal cancer stem cell…
By newseditor
Posted 16 Jun
Paranoia in the brain
By newseditor
Posted 16 Jun
In-vitro 3D culture of func…
By newseditor
Posted 15 Jun
Neural balance in the brain…
By newseditor
Posted 15 Jun
Antimalarial compounds reli…
By newseditor
Posted 15 Jun
Other Top Stories
Linking mossy brain cells to seizures and memory loss
Read more
Graphene membranes used to purify water
Read more
A transcription factor controls bone health and prevents osteoarthr…
Read more
Video games to improve mobility after a stroke
Read more
Calcium-synuclein interaction and neurodegenerative diseases
Read more
Protocols
Bioengineered human colon o…
By newseditor
Posted 14 Jun
Development of an efficient…
By newseditor
Posted 12 Jun
A co-culture system of macr…
By newseditor
Posted 10 Jun
Analysis of 3D pathology sa…
By newseditor
Posted 08 Jun
Long-term expandable mouse…
By newseditor
Posted 07 Jun
Publications
Innate-like T cells in live…
By newseditor
Posted 16 Jun
Membrane to cortex attachme…
By newseditor
Posted 16 Jun
NRG1-ErbB4 signaling in the…
By newseditor
Posted 15 Jun
HPV integration and cervica…
By newseditor
Posted 15 Jun
Cerebral tau pathology in c…
By newseditor
Posted 15 Jun
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
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
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