Research Spotlight: Large-Scale Study Identifies 600 Regions in Genome that Affect Type 2 Diabetes Risk

As part of an international team of scientists, Jose Mercader Bigas, PhD, an investigator in the Diabetes Unit at Massachusetts General Hospital and instructor in Medicine at Harvard Medical School, and Group Leader at the Broad Institute is co-senior author of a new study in Nature, Multi-Ancestry Genome Wide Study in >2.5 million Individuals Reveals Heterogeneity in Mechanistic Pathways of Type 2 Diabetes and Complications.

Additional authors from Massachusetts General Hospital include Ravi Mandla, Alicia Huerta, Aaron Leong, Vicky Kaur, Miriam Udler, James Meigs and Jose C. Florez.

Leading institutions include the University of Manchester, the Helmholtz Institute of Translational Genomics, the National Human Genome Research Institute, the University of Michigan, the University of Pennsylvania and UCLA.

Summary:

International collaborations and data sharing mechanisms are essential to identify genetic risk variants that modify the risk of type 2 diabetes.

Scientists at Massachusetts General Hospital, and the Broad Institute are part of the newly formed Type 2 Diabetes Global Genomics Initiative (T2D-GGI). The study encompasses 2.5 million individuals in which millions of genetic variants have been tested for association with type 2 diabetes.

They have identified over 600 regions in the genome that are associated with modified risk for the disease. These findings can be used to improve prediction and develop preventive strategies for type 2 diabetes and to identify new drug targets to treat the disease.

What Question Did You Set Out to Answer?

Which are the genetic variants that modify risk of type 2 diabetes?

What Approach Did You Use?

An international team of scientists conducted a comprehensive study with data from millions of individuals. The newly formed Type 2 Diabetes Initiative (T2D-GGI) has produced the largest genome-wide association study (GWAS) meta-analysis to date.

By aggregating data from nearly 100 studies, the new study encompasses over 2.5M individuals including 428,452 with T2D).

These genetic risk scores have to be carefully interpreted in the context of the already established clinical risk factors for type 2 diabetes.

What Are the Clinical Implications?

The results represent a major breakthrough and an opportunity to generate genetic risk scores that could be used to allow prediction, early diagnosis and prevention of type 2 diabetes.

What Are the Next Steps?

The next step is to understand how these variants contribute to type 2 diabetes and their complications.

The results, which will become available to the research community, will allow other researchers in the world to investigate these variants and genes close to these variants to increase the understanding of type 2 diabetes and identify novel drug targets to treat or prevent the disease.

Paper Cited:

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. MGH is a founding member of the Mass General Brigham healthcare system.