The Broad Institute of MIT and Harvard

Academic Institute

OFHS260006

Diabetes is one of the biggest health challenges of this century. About 1 in every 250 people with diabetes has it because of rare gene changes that have a very strong effect. Many more people carry rare gene changes that have a moderate effect, but these often don’t show up in standard genetic test reports. In this project, we will study the largest collection ever assembled of rare genetic differences - data from more than one million people (including participants from Our Future Health) from many backgrounds. Our goal is to better understand how these rare gene changes affect a person’s risk of developing diabetes. We will combine this information with lab experiments and real world clinical data from patients to create a new way to evaluate and communicate genetic risk. This work will help improve how genetic results are reported in healthcare and support more accurate, personalized diabetes care for people from all populations. Some types of diabetes are caused by a single gene change. These cases make up about 2 to 6% of diabetes that begins in childhood and are caused by rare genetic variants that have a strong effect. Many of these cases are never diagnosed, especially in people from non European backgrounds. Because this form of diabetes can be treated using precision medicine - treatments tailored to a person’s specific gene change – these missed diagnoses create health inequalities for non European populations. It is hard to tell whether a rare genetic variant causes diabetes when the person comes from a group that is under represented in genetic databases. There is a need for a single, consistent system, with updated guidelines, for how rare genetic variants should be interpreted, classified, and reported for diagnostic and screening purposes. To improve how rare variants are interpreted, we aim to build the largest dataset from 1.1 million people, one third of whom are from non European backgrounds (including Our Future Health), and aim to show how including genetic data from diverse populations can improve the diagnosis of different types of diabetes and support precision medicine for everyone.

Diabetes caused by a change in a single gene affects about 3.1 million people worldwide, and getting the right diagnosis can help them receive the treatment that works best for them. This matters for patients themselves but also for their families, including during pregnancy. This project will provide a framework for variant classification, interpretation and reporting of these rare genetic variants in patients with severe forms of diabetes. While these rare genetic changes can increase someone’s risk of diabetes and can sometimes guide treatment, they are not always reported consistently by medical testing labs. Our project will review and update the classification of rare genetic changes that are currently labelled as “uncertain,” which will help doctors make more accurate diagnoses for people who may have rare forms of diabetes. This work will benefit people from non-European backgrounds, who are more likely to receive an incorrect diagnosis because there is not enough genetic information available for their populations. By building the largest dataset from 1.1 million people, one third of whom are from non European backgrounds (including Our Future Health), we will be able to properly understand and explain rare genetic changes that are more common in these groups.

Public Health Research

04/08/2026

10/06/2026

TRE