Large-Sample Study Links Rare DNA Variations to Type 2 Diabetes

An international team of researchers linked a number of rare DNA alternations to type 2 diabetes (T2D), according to their findings published in Nature. 

In this study, researchers assessed gene data from 42,800 individuals from five self-reported ancestral backgrounds: 33.8% Hispanic/Latino (n=14,442), 24.6% European (n=10,517), 13.9% African-American (n=5,959), 14.1% East-Asian (n=6,010), and 13.6% South-Asian (n=5,833). Each group yielded equivalent statistical power, and the study tested an augmented population number compared to a previous exome-sequencing study of 6,504 T2D patients and 6,436 controls. In total, this current study evaluated approximately 21,000 individuals with T2D and 25,000 healthy controls.  

Results Provide ‘An Updated Picture’ 

According to the study results, the researchers detected four genes with variants associated with increased diabetes risk. “These results demonstrate the importance of studying large samples of individuals from a wide range of ancestries,” said senior study author Michael Boehnke, professor of biostatistics and director of the Center for Statistical Genetics at the University of Michigan School of Public Health, in a press release about the study. “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 Jason Flannick, 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.” Flannick is an assistant professor of pediatrics at Harvard Medical School and the Division of Genetics and Genomics at Boston Children’s Hospital, and an associate member of the Broad Institute of MIT and Harvard. 

Increased Sample Sizes Are Needed 

The researchers hypothesize that a larger cohort, with sample sizes ranging between 75,000 and 185,000 cases may be required to elucidate their findings, and that the increased sample sizes can potentially detect additional variant genes. 

“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,” said  Dr. Jose Florez, chief of the endocrine division and diabetes unit at Massachusetts General Hospital, a professor of medicine at Harvard Medical School, and director of the diabetes research group at the Broad Institute. “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.” 

Source: Nature, EurekAlert