An international consortium of researchers has analyzed protein coding genes from nearly 46,000 people who associate rare DNA changes with type 2 diabetes. The study, one of the largest known of its kind, contains data from people from European, African American, Latin American, Latin American, East Asian and South Asian ancestors.
From this large cohort ̵
These genes and proteins they encode are potential targets for new drugs and can lead researchers to better understand and treat disease.
All Team Results are publicly available online through Type 2 Diabetes Knowledge Portal, which allows researchers around the world to access and use the information for their own research.
"These results show that it is important to study large samples of people from a wide range of ancestors," says senior researcher Michael Boehnke, professor of biostatistics and director of the Center for Statistical Genetics at the University of Michigan School of Public Health. Most major population studies focus on individuals of European ancestors, and it can make it difficult to generalize the results globally. The more diversified the cohort gives better and more informative science. "
" We now have an updated picture of the role of rare DNA variations in diabetes, "said Jason Flannick, first author of the study." These rare variants potentially allow a much more valuable resource for drug development than previously assumed. We can actually find evidence of their disease association in many genes that could be targeted by new drugs or studied to understand the basic processes underlying the disease. "Flannick is an assistant professor of paediatrics at Harvard Medical School and Division of Genetics and Genomics at Boston Children's Hospital and an Associate Member of the Broad Institute of MIT and Harvard.
Other senior authors include Mark McCarthy, Professor of Diabetic Medicine at the University of Oxford and Jose Florez, Head of the Endocrine Division and Diabetes Unit at Massachusetts General Hospital, Professor of Medicine at Harvard Medical School and Director of the Diabetes Research Group at Broad Institute.
The study was published today in Nature .
A Global Concern  According to statistics from the World Health Organization, over 400 million people worldwide have diabetes most cases are type 2. Diabetes is considered to be the seventh leading cause of death globally. While researchers have known that lifestyle and environmental factors play a major role in type 2 diabetes, it is important to gain a deeper understanding of the biological mechanisms that drive the condition.
For this study, the researchers sequenced what is called "exome," that is, only those regions of the genome that encode proteins.
Another approach to finding disease-associated variants is called a linked association study or GWAS. This approach may be very effective in finding common-disease variants throughout the genome, but may miss the less common exome variants. And this is the key because, while rare exome variants are extremely difficult to detect, they can provide invaluable insights into disease-related genes, which in turn can suggest new drug targets.
Therefore, researchers are looking to increase plug sizes in future studies. With a cohort of nearly 50,000, this may be the largest exome sequencing study of type 2 diabetes, but as the authors point out, sample sizes of between 75,000 and 185,000 cases may be needed to identify even the rare variants with the greatest impact. .
"It is critical to remember that just because we are studying variants in protein coding DNA, we do not pause the number of samples needed to detect a significant effect," says Jose Florez. "The effects of these variations can be powerful, but because they are so rare, we still need to increase the sample size to really derive compelling insights."
First Recovered Association Study (GWAS) for Type 2 Diabetes in Youth Results
Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls, Nature (2019). DOI: 10.1038 / s41586-019-1231-2, https://www.nature.com/articles/s41586-019-1231-2
Massive sequencing studies rare DNA changes in type 2 diabetes (2019, May 22)
May 23, 2019
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