Understanding that diet and exercise are modifiable risk factors involved in the development of type 2 diabetes (T2D), researchers are now exploring the role of genes as nonmodifiable risk factors contributing to disease emergence. Lead author of a 23andMe white paper and Senior Product Scientist, Michael L. Multhaup, PhD, and colleagues set out to answer that question.  

Dr. Multhaup presented his research, titled “Polygenic Risk Score Predicts Type 2 Diabetes Susceptibility in a Diverse Consumer Genetic Database,” at the American Diabetes Association’s Annual Conference on June 10 in San Francisco. According to Anne Wojcicki, CEO and cofounder of 23andMe, “Diabetes is a significant health issue in the United States that is expected to impact nearly half of the population.” She added, “When customers learn about their genetic likelihood of developing type 2 diabetes, we believe there is an opportunity to motivate them to change their lifestyle and ultimately to help them prevent the disease.”

The research team explored genetic risk, which has become an increasingly relevant predictive factor for the development of T2D given that the heritability of this illness is estimated at a wide range of 25% to 75%. Building on these known factors, the research team evaluated multiple genetic markers using 23andMe’s extensive customer DNA database, which includes over 600,000 consenting participants who self-disclosed their personal diabetes diagnosis. 

According to the team, the polygenic score methodology used to develop this report was based on a previously validated computational pipeline appropriate for building polygenic scores that is calculated based on more than 1,000 genetic variants. Using logistical regression, associations were evaluated based on genetic variants as predictors, such as age, sex, genetic principal components, and genotyping date. The calculated score determines the degree to which genetics may contribute to developing T2D, in addition to other diseases. 

As reported by Eloycsia Ratliff, MPH, 23andMe Medical Education project manager, “Our researchers then tested the performance of the polygenic score in separate sets of participants to cover five different ancestries—African-American, East-Asian, European, Latino, and South Asian. Based on the results, 23andMe researchers were able to make associations between an individual’s genetics and their likelihood of developing T2D. Researchers categorized results into ‘increased likelihood’ and ‘typical likelihood,’ where an ‘increased likelihood’ result means the likelihood of developing T2D from genetics alone exceeds the likelihood of developing the condition due to being overweight.” 

While the authors acknowledge several limitations to their study, they underscore the importance of their work by aiming to investigate the generalizability of their model as well as the absolute risk estimates. They conclude that the rapidly growing database will allow continued improvement using the polygenic score in the future, and they are committed to updating and improving the polygenic score model as well as monitoring the accuracy of the data used to predict these scores. 
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